Metabolites from Alternaria Fungi and Their Bioactivities
MOA Key Laboratory of Plant Pathology, Department of Plant Pathology, College of Agronomy and Biotechnology, China Agricultural University, Beijing 100193, China
*
Author to whom correspondence should be addressed.
Molecules 2013, 18(5), 5891-5935; https://doi.org/10.3390/molecules18055891
Submission received: 18 March 2013
/
Revised: 6 May 2013
/
Accepted: 16 May 2013
/
Published: 21 May 2013
(This article belongs to the Section Natural Products Chemistry)
Abstract
:Alternaria is a cosmopolitan fungal genus widely distributing in soil and organic matter. It includes saprophytic, endophytic and pathogenic species. At least 268 metabolites from Alternaria fungi have been reported in the past few decades. They mainly include nitrogen-containing metabolites, steroids, terpenoids, pyranones, quinones, and phenolics. This review aims to briefly summarize the structurally different metabolites produced by Alternaria fungi, as well as their occurrences, biological activities and functions. Some considerations related to synthesis, biosynthesis, production and applications of the metabolites from Alternaria fungi are also discussed.
1. Introduction
Alternaria fungi, belonging to the Dematiaceae of the Hyphomycetes in the Fungi Imperfecti, have a widespread distribution in Nature. They act as plant pathogens, weak facultative parasites, saprophytes and endophytes [1]. Some metabolites from Alternaria fungi are toxic to plants and animals, and are designated as phytotoxins and mycotoxins, respectively [2,3,4]. Alternaria metabolites exhibit a variety of biological activities such as phytotoxic, cytotoxic, and antimicrobial properties, which have drawn the attention of many chemists, pharmacologists, and plant pathologists in research programs as well as in application studies [5,6]. For examples, porritoxin (21, Table 1) from endophytic Alternaria species has been studied as the candidate of cancer chemoproventive agent [7]. Depudecin (257), an inhibitor of histone deacetylase (HDAC) from A. brassicicola, also showed its antitumor potency [8,9]. Some Alternaria metabolites such as tenuazonic acid (15), maculosin (43) and tentoxin (53) have been studied as the herbicide candidates [10,11,12].
In the early 1990s, about 70 metabolites from Alternaria fungi were reviewed [13]. Several reviews on Alternaria phytotoxins have been published over the last few decades [6,14,15]. In recent years, more and more metabolites with bioactivities from Alternaria fungi have been isolated and structurally characterized. This review mainly presents classification, occurrences, biological activities and functions of the metabolites from Alternaria fungi. We also discussed and prospected the synthesis, biosynthesis, production and applications of the metabolites from Alternaria fungi.
2. Classification and Occurrence
The metabolites from Alternaria fungi can be grouped into several categories which include nitrogen-containing compounds, steroids, terpenoids, pyranones (pyrones), quinones, phenolics, etc. Several metabolites are unique to one Alternaria species, but most metabolites are produced by more than one species. Occurrences of the isolated metabolites from Alternaria fungi are listed in Table 1 [16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134,135]. The most widespread metabolite is alternariol (157) which has been isolated from a few Alternaria fungi [25,27,84,85]. Some metabolites were also isolated from other genus fungi and even from higher plants. Typical examples included AAL toxins 3–10 from Fusarium species [5,136,137], helvolic acid (117) from Aspergillus species [138] and Pichia species [139], paclitaxel (taxol, 61) from yew trees (Taxus spp.) [140], resveratrol (252) from a variety of plant species such as Vitis vinifera, Polygonum cuspidatum and Glycine max [141], besides these metabolites from Alternaria species [43,53,130].
| Metabolite class | Metabolite name | Alternaria species | Reference |
|---|---|---|---|
| Nitrogen-containing Metabolites | AAL-toxin TA1 (1) | A. alternata f.sp. lycopersici | [16,17] |
| AAL-toxin TA2 (2) | A. alternata f.sp. lycopersici | [16,17] | |
| AAL-toxin TB1 (3) | A. alternata f.sp. lycopersici | [16,17] | |
| AAL-toxin TB2 (4) | A. alternata f.sp. lycopersici | [16,17] | |
| AAL-toxin TC1 (5) | A. alternata f.sp. lycopersici | [18] | |
| AAL-toxin TC2 (6) | A. alternata f.sp. lycopersici | [18] | |
| AAL-toxin TD1 (7) | A. alternata f.sp. lycopersici | [18] | |
| AAL-toxin TD2 (8) | A. alternata f.sp. lycopersici | [18] | |
| AAL-toxin TE1 (9) | A. alternata f.sp. lycopersici | [18] | |
| AAL-toxin TE2 (10) | A. alternata f.sp. lycopersici | [18] | |
| Fumonisin B1 (11) | A. alternata | [19] | |
| A. alternata f.sp. lycopersici | [20] | ||
| Altersetin (12) | Alternaria sp. | [21] | |
| N-Acetyltyramine (13) | A. tenuissima | [22] | |
| Pyrophen (14) | A. alternata | [23] | |
| Tenuazonic acid = TeA = TA = AAC-toxin (15) | A. alternata | [24,25,26,27,28] | |
| A. citri | [29] | ||
| A, crassa | [30] | ||
| A. linicola | [31] | ||
| A. tenuissima | [24] | ||
| Deprenylzinnimide (16) | A. porri | [32] | |
| Zinnimide (17) | A. porri | [32] | |
| Cichorine (18) | A. cichorii | [33] | |
| Zinnimidine (19) | A. cichorii | [33] | |
| A. porri | [32,34,35] | ||
| Z-Hydroxyzinnimidine (20) | A. cichorii | [33] | |
| Porritoxin (21) | A. porri | [7,36] | |
| Porritoxin sulfonic acid (22) | A. porri | [35] | |
| ACT-toxin I (23) | A. alternata | [37,38] | |
| ACT-toxin II (24) | A. alternata | [37,38] | |
| AK-toxin I (25) | A. kikuchiana (A. alternata) | [39] | |
| AK-toxin II (26) | A. kikuchiana (A. alternata) | [39] | |
| AS-I toxin (27) | A. alternata | [40] | |
| (2S,3S,4R,2'R)-2-(2'-hydroxytetracosanoylamino) Octadecane-1,3,4-triol (28) | Alternaria sp. | [41] | |
| Cerebroside B (29) | Alternaria sp. | [41] | |
| Cerebroside C (30) | Alternaria sp. | [41] | |
| AI-77-B (31) | A. tenuis | [42] | |
| AI-77-F (32) | A. tenuis | [42] | |
| Sg17-1-4 (33) | A. tenuis | [42] | |
| Cyclo-(Pro-Ala-) (34) | A. alternata | [10] | |
| A. tenuissima | [22] | ||
| Nitrogen-containing Metabolites | Cyclo-(Pro-Pro-) (35) | A. tenuissima | [22] |
| Cyclo-(Phe-Ser-) (36) | Alternaria sp.FL25 | [43] | |
| Cyclo-(l-Leu-trans-4-hydroxy-l-Pro-) (37) | A. alternata | [44] | |
| A. tenuissima | [22] | ||
| Cyclo-(S-Pro-R-Val-) (38) | A. alternata | [10] | |
| A. tenuissima | [22] | ||
| Cyclo-(Pro-Leu-) (39) | A. tenuissima | [22] | |
| Cyclo-(Pro-Homoleucine-) (40) | A. alternata | [10] | |
| Cyclo-(S-Pro-R-Ile-) (41) | A. tenuissima | [22] | |
| Cyclo-(Pro-Phe-) (42) | A. alternata | [10] | |
| A. tenuissima | [22] | ||
| Maculosin = Cyclo-(l-Pro-l-Tyr-) (43) | A. alternata | [10] | |
| Cyclo-(l-Phe-trans-4-hydroxy-l-Pro-) (44) | A. alternata | [44] | |
| Cyclo-(l-Ala-trans-4-hydroxy-L-Pro-) (45) | A. alternata | [44] | |
| AM-toxin I (46) | A. mali (A. alternata) | [39] | |
| AM-toxin II (47) | A. mali (A. alternata) | [39] | |
| AM-toxin III (48) | A. mali (A. alternata) | [39] | |
| Destruxin A (49) | A. linicola | [31] | |
| Destruxin B (50) | A. brassicae | [45] | |
| A. linicola | [31] | ||
| Homodestruxin B (51) | A. brassicae | [46] | |
| Desmethyldestruxin B (52) | A. brassicae | [46] | |
| Tentoxin (53) | A. alternata | [47] | |
| A. citri | [29] | ||
| A. linicola | [31] | ||
| A. porri | [48] | ||
| Isotentoxin (54) | A. porri | [48] | |
| Dihydrotentoxin (55) | A. citri | [29] | |
| A. porri | [47,48] | ||
| Uridine (56) | A. alternata | [49] | |
| Adenosine (57) | A. alternata | [49] | |
| Brassicicolin A (58) | A. brassicicola | [50,51] | |
| Fumitremorgin B (59) | Alternaria sp. FL25 | [52] | |
| Fumitremorgin C (60) | Alternaria sp. FL25 | [52] | |
| Paclitaxel = Taxol (61) | A. alternata var. monosporus | [53] | |
| Steroids | Ergosterol (62) | A. alternata | [27,54] |
| Ergosta-4,6,8(14),22-tetraen-3-one (63) | A. alternata | [27,54] | |
| Ergosta-4,6,8(9),22-tetraen-3-one (64) | A.alternata | [49] | |
| Ergosta-7,24(28)-dien-3-ol ( 65 ) | A. alternata | [49] | |
| 3β-Hydroxy-ergosta-5,8(9),22-trien-7-one (66) | A. brassicicola ML-P08 | [55] | |
| 3β,5α-Dihydroxy-ergosta-7,22-dien-6-one (67) | A. brassicicola ML-P08 | [55] | |
| Cerevisterol (68) | A. brassicicola ML-P08 | [55] | |
| Terpenoids | Bicycloalternarene 1 (69) | A. alternata | [56] |
| Bicycloalternarene 11 (70) | A. alternata | [56] | |
| Bicycloalternarene 2 (71) | A. alternata | [56] | |
| Bicycloalternarene 3 = ACTG toxin A (72) | A. alternata | [56] | |
| Bicycloalternarene 4 (73) | A. alternata | [56] | |
| Bicycloalternarene 10 (74) | A. alternata | [56] | |
| Bicycloalternarene 5 (75) | A. alternata | [56] | |
| Bicycloalternarene 8 (76) | A. alternata | [56] | |
| Bicycloalternarene 9 = ACTG toxin B (77) | A. alternata | [56] | |
| Bicycloalternarene 6 (78) | A. alternata | [56] | |
| Bicycloalternarene 7 (79) | A. alternata | [56] | |
| Tricycloalternarene 1a (80) | A. alternata | [57] | |
| Tricycloalternarene 1b (81) | A. alternata | [57,58] | |
| Tricycloalternarene 11a (82) | A. alternata | [59] | |
| Tricycloalternarene 11b (83) | A. alternata | [59] | |
| Tricycloalternarene 2a (84) | A. alternata | [57] | |
| Tricycloalternarene 2b (85) | A. alternata | [57,58] | |
| Tricycloalternarene 3a (86) | A. alternata | [57] | |
| Tricycloalternarene 3b = ACTG toxin G (87) | A. alternata | [57,60] | |
| A. citri | [61] | ||
| ACTG toxin H (88) | A. citri | [61] | |
| Tricycloalternarenal (89) | A. alternata | [60] | |
| Tricycloalternarene 4a (90) | A. alternata | [57] | |
| Tricycloalternarene 4b (91) | A. alternate | [57] | |
| Tricycloalternarene 10b (92) | A. alternate | [59] | |
| Tricycloalternarene 5a (93) | A. alternate | [57] | |
| Tricycloalternarene 5b (94) | A. alternate | [57] | |
| Tricycloalternarene 8a (95) | A. alternate | [59] | |
| Tricycloalternarene 9b (96) | A. alternate | [59] | |
| Tricycloalternarene 6a (97) | A. alternate | [59] | |
| Tricycloalternarene 6b (98) | A. alternate | [59] | |
| Tricycloalternarene 7a (99) | A. alternate | [59] | |
| Tricycloalternarene 7b (100) | A. alternate | [59] | |
| Tricycloalternarene A (101) | A. alternata Ly83 | [58] | |
| Tricycloalternarene B (102) | A. alternata Ly83 | [58] | |
| Tricycloalternarene C (103) | A. alternata Ly83 | [58] | |
| Tricycloalternarene D (104) | A. alternata Ly83 | [58] | |
| Tricycloalternarene E (105) | A. alternata Ly83 | [58] | |
| Brassicicene A (106) | A. brassicicola | [62] | |
| Brassicicene B (107) | A. brassicicola | [62] | |
| Brassicicene C (108) | A. brassicicola | [62] | |
| Brassicicene D (109) | A. brassicicola | [62] | |
| Brassicicene E (110) | A. brassicicola | [62] | |
| Brassicicene F (111) | A. brassicicola | [62] | |
| Brassicicene G (112) | A. brassicicola | [51] | |
| Brassicicene H (113) | A. brassicicola | [51] | |
| Brassicicene I (114) | A. brassicicola | [51] | |
| Abscisic acid = ABA (115) | A. brassicae | [63] | |
| (1aS,2S,6R,7R,7aR,7bR)-1a,2,4,5,6,7,7a,7b-Octahydro-7,7a-dimethyl-1a-(1-methylethenyl)-naphth[1,2-b]oxirene-2,6-diol (116) | A. citri | [61] | |
| Helvolic acid (117) | Alternaria sp. FL25 | [43] | |
| Pyranones | Radicinin (118) | A. chrysanthemi | [64,65] |
| A. helianthi | [66] | ||
| A. radicina | [67] | ||
| Deoxyradicinin (119) | Alternaria sp. CIB 108 | [68] | |
| A. helianthi | [66,69] | ||
| Radicinol (120) | A. chrysanthemi | [64,65] | |
| A. radicina | [67] | ||
| Deoxyradicinol (121) | A. helianthi | [66] | |
| 3-Epiradicinol (122) | Alternaria sp. CIB 108 | [68] | |
| A. chrysanthemi | [65] | ||
| A. radicina | [67] | ||
| 3-Epideoxyradicinol (123) | Alternaria sp. CIB 108 | [68] | |
| A. helianthi | [70] | ||
| 3-Methoxy-3-epiradicinol (124) | A. chrysanthemi | [65] | |
| 9,10-Epoxy-3-methoxy-3-epiradicinol (125) | A. chrysanthemi | [65] | |
| Radianthin (126) | A. helianthi | [66] | |
| 3-Butyryl-6-[rel-(1S,2S)-1,2-dihydroxypropyl]-4-hydroxy-2H-pyran-2-one (127) | Alternaria sp. CIB 108 | [68] | |
| Phomapyrone A = Phomenenin A (128) | A. brassicicola | [51] | |
| A. infectoria | [71] | ||
| Phomenenin B (129) | A. infectoria | [71] | |
| Phomapyrone G (130) | A. brassicicola | [51] | |
| Infectopyrone (131) | A.arbusti | [72] | |
| A. conjuncta | [72] | ||
| A. infectoria | [72,73] | ||
| A. intercepta | [72] | ||
| A. metachromatica | [72] | ||
| A. novae-zelandiae | [72] | ||
| A. oregonensis | [72] | ||
| A. triticimaculans | [72] | ||
| A. viburni | [72] | ||
| Herbarin A (132) | A. brassicicola ML-P08 | [55] | |
| Alternaric acid (133) | A. solani | [74] | |
| Novae-zelandin A (134) | A. cetera | [72] | |
| A. infectoria | [72] | ||
| A. intercepta | [72] | ||
| A. novae-zelandiae | [72] | ||
| A. triticimaculans | [72] | ||
| A. viburni | [72] | ||
| Novae-zelandin B (135) | A. cetera | [72] | |
| A. infectoria | [72] | ||
| A. intercepta | [72] | ||
| A. novae-zelandiae | [72] | ||
| A. triticimaculans | [72] | ||
| A. viburni | [72] | ||
| 4 Z-Infectopyrone (136) | A. arbusti | [72] | |
| A. conjuncta | [72] | ||
| A. infectoria | [72] | ||
| A. intercepta | [72] | ||
| A. metachromatica | [72] | ||
| A. novae-zelandiae | [72] | ||
| A. oregonensis | [72] | ||
| A. triticimaculans | [72] | ||
| A. viburni | [72] | ||
| Pyrenocine A (137) | A. infectoria | [72] | |
| Pyrenocine B (138) | A. infectoria | [72] | |
| Pyrenocine C (139) | A. infectoria | [72] | |
| ACRL toxin I (140) | A. citri | [75] | |
| ACRL toxin II (141) | A. citri | [76] | |
| ACRL toxin III (142) | A. citri | [76] | |
| ACRL toxin IV (143) | A. citri | [76] | |
| ACRL toxin IV’ (144) | A. citri | [76] | |
| Solanapyrone A (145) | A. solani | [77] | |
| Solanapyrone B (146) | A. solani | [77] | |
| Solanapyrone C (147) | A. solani | [77] | |
| Solanapyrone D (148) | A. solani | [78] | |
| Solanapyrone E (149) | A. solani | [78] | |
| Tenuissimasatin (150) | A. tenuissima | [22] | |
| Altechromone A (151) | A. brassicicola ML-P08 | [55] | |
| 2,5-Dimethyl-7-hydroxychromone (152) | Alternaria sp. | [79] | |
| Phomapyrone F (153) | A. brassicicola | [51] | |
| Altenuisol (154) | Alternaria sp. | [80] | |
| A. tenuis | [81] | ||
| Altertenuol (155) | A. tenuis | [82] | |
| Dehydroaltenusin (156) | A. tenuis | [83] | |
| Alternariol =AOH (157) Alternariol 5-O-sulfate (158) | Alternaria sp. | [41,84] | |
| A. alternata | [25,27,85] | ||
| Alternaria sp. | [84] | ||
| Alternariol 9-methyl ether = AME = Djalonensone (159) | Alternaria sp. | [41,84,86] | |
| A. alternata | [25,27,85] | ||
| A. linicola | [31] | ||
| A. tenuis | [87] | ||
| A. tenuissima | [86] | ||
| Alternariol 5-O-methyl ether-4'-O-sulfate (160) | Alternaria sp. | [84] | |
| 3'-Hydroxyalternariol (161) | Alternaria sp. | [84] | |
| Altenuene = ATL (162) | Alternaria sp. | [84] | |
| A. alternata | [85] | ||
| Isoaltenuene (163) | A. alternata | [88] | |
| 4'-Epialtenuene (164) | Alternaria sp. | [84] | |
| 5'-Epialtenuene (165) | A. alternata | [89] | |
| Neoaltenuene (166) | A. alternata | [89] | |
| Rubrofusarin B (167) | A. alternata | [23] | |
| Fonsecin (168) | A. alternata | [23] | |
| Fonsecin B (169) | A. alternata | [23] | |
| Aurasperone A (170) | A. alternata | [23] | |
| Aurasperone B (171) | A. alternata | [23] | |
| Aurasperone C (172) | A. alternata | [23] | |
| Aurasperone F (173) | A. alternata | [23] | |
| Quinones | Macrosporin (174) | Alternaria sp. ZJ-2008003 | [90] |
| A. porri | [32] | ||
| A. solani | [91] | ||
| Demethylmacrosporin (175) | A. porri | [32] | |
| Dihydroaltersolanol A (176) | Alternaria sp. ZJ-2008003 | [90] | |
| Tetrahydroaltersolanol B (177) | Alternaria sp. ZJ-2008003 | [90] | |
| A. solani | [92] | ||
| Tetrahydroaltersolanol C (178) | Alternaria sp. ZJ-2008003 | [90] | |
| Tetrahydroaltersolanol D (179) | Alternaria sp. ZJ-2008003 | [90] | |
| Tetrahydroaltersolanol E (180) | Alternaria sp. ZJ-2008003 | [90] | |
| Tetrahydroaltersolanol F (181) | Alternaria sp. ZJ-2008003 | [90] | |
| Bostrycin (182) | A. eichhorniae | [93] | |
| 4-Deoxybostrycin (183) | A. eichhorniae | [93] | |
| Hydroxybostrycin (184) | A. solani | [94] | |
| Altersolanol A = Stemphylin (185) | A. porri | [95] | |
| A. solani | [94,96,97] | ||
| Altersolanol B = Dactylarin (186) | Alternaria sp. ZJ-2008003 | [90] | |
| A. porri | [95] | ||
| A. solani | [94,96,97] | ||
| Altersolanol C = Dactylariol (187) | Alternaria sp. ZJ-2008003 | [90] | |
| A. porri | [95,98] | ||
| A. solani | [94,96,97] | ||
| Altersolanol D (188) | A. solani | [94,96,97] | |
| Altersolanol E (189) | A. solani | [94,96,97] | |
| Altersolanol F (190) | A. solani | [94,96,97] | |
| Altersolanol G (191) | A. solani | [94] | |
| Altersolanol H (192) | A. solani | [94] | |
| Altersolanol L (193) | Alternaria sp. ZJ-2008003 | [90] | |
| Ampelanol (194) | Alternaria sp. ZJ-2008003 | [90] | |
| Alterporriol A/B (195) | A. porri | [32] | |
| A. solani | [94,99] | ||
| Alterporriol C (196) | Alternaria sp. ZJ-2008003 | [90] | |
| A. porri | [32] | ||
| A. solani | [99] | ||
| Alterporriol D/E (197) | A. porri | [32] | |
| Alterporriol F (198) | A. porri | [32] | |
| Alterporriol K (199) | Alternaria sp. ZJ9-6B | [100] | |
| Alterporriol L (200) | Alternaria sp. ZJ9-6B | [100] | |
| Alterporriol M (201) | Alternaria sp. ZJ9-6B | [100] | |
| Alterporriol N (202) | Alternaria sp. ZJ-2008003 | [90] | |
| Alterporriol O (203) | Alternaria sp. ZJ-2008003 | [90] | |
| Alterporriol P (204) | Alternaria sp. ZJ-2008003 | [90] | |
| Alterporriol Q (205) | Alternaria sp. ZJ-2008003 | [90] | |
| Alterporriol R (206) | Alternaria sp. ZJ-2008003 | [90] | |
| Alterperylenol (207) | Alternarial sp. | [79,101] | |
| Alternaria sp. M6 | [102] | ||
| A. alternata | [27] | ||
| A. cassiae | [103] | ||
| A. tenuissima | [22] | ||
| 8β-Chloro-3,6aα,7β,9β,10-pentahydroxy-9,8,7,6a-tetrahydroperylen-4(6aH)-one (208) | Alternaria sp. M6 | [102] | |
| Dihydroalterperylenol (209) | Alternarial sp. | [101] | |
| Alternaria sp. M6 | [102] | ||
| A. alternate | [104] | ||
| Stemphyperylenol (210) | Alternaria sp. | [79] | |
| A. alternata | [105] | ||
| A. cassiae | [103] | ||
| 6-Epi-stemphytriol (211) | A. alternata | [105] | |
| Altertoxin I = ATX-I (212) | Alternaria sp. | [79,80,106] | |
| A. alternata | [26,27,104,105,107] | ||
| A. cassiae | [103] | ||
| A. tenuissima | [22] | ||
| Alteichin (213) | A. alternata | [26,107] | |
| A. eichorniae | [108] | ||
| Alterlosin I (214) | A. alternata | [26] | |
| Alterlosin II (215) | A. alternata | [26] | |
| Phenolics | p-Hydroxybenzoic acid (219) | A. tagetica | [109] |
| Tyrosol (220) | A. tagetica | [109] | |
| α-Acetylorcinol (221) | A. tenuissima | [22] | |
| 2-Carboxy-3-(2-hydroxypropanyl) phenol (222) | Alternaria sp. HS-3 | [110] | |
| Methyl eugenol (223) | Alternaria sp. | [111] | |
| Tagetolone (224) | A. tagetica | [109] | |
| Tagetenolone (225) | A. tagetica | [109] | |
| Zinniol (226) | A. carthami | [112,113] | |
| A. cichorii | [33] | ||
| A. cirsinoxia | [114] | ||
| A. dauci | [115] | ||
| A. macrospora | [113] | ||
| A. porri | [113,116] | ||
| A. solani | [113,117,118] | ||
| A. tagetica | [113,116,119] | ||
| A. zinniae | [120] | ||
| 8-Zinniol 2-(phenyl)-ethyl ether (227) | A. solani | [118] | |
| A. tagetica | [116] | ||
| 8-Zinniol methyl ether (228) | A. solani | [118] | |
| A. tagetica | [116] | ||
| 8-Zinniol acetate (229) | A. tagetica | [116] | |
| 7-Zinniol acetate (230) | A. tagetica | [116] | |
| Homozinniol (231) | A. solani | [117] | |
| Zinnol (232) | A. cichorii | [33] | |
| 8-Zinnol methyl ether (233) | A. solani | [118] | |
| A. tagetica | [116] | ||
| Zinnidiol (234) | A. cichorii | [33] | |
| 2-(2'',3''-dimethyl-but-1-enyl)-Zinniol (235) | A. solani | [118] | |
| Bis-7-O-8''.8-O-7''-zinniol (236) | A. tagetica | [121] | |
| Bis-7-O-7''.8-O-8''-zinniol (237) | A. tagetica | [121] | |
| 4-Acetyl-5-hydroxy-3,6,7-trimethylbenzofuran-2(3 H)-one (238) | Alternaria sp. HS-3 | [110] | |
| 5-Methyl-6-hydroxy-8-methoxy-3-methylisochroman (239) | Alternaria sp. HS-3 | [110] | |
| Alternarian acid (240) | Alternaria sp. | [79] | |
| Altenusin (241) | Alternaria sp. | [79,84,122,123] | |
| A. mali | [124] | ||
| A. tenuis | [82] | ||
| Desmethylaltenusin (242) | Alternaria sp. | [84] | |
| Porric acid D (243) | Alternaria sp. | [123] | |
| Alterlactone (244) | Alternaria sp. | [84] | |
| Alternethanoxin A (245) | A. sonchi | [125] | |
| Alternethanoxin B (246) | A. sonchi | [125] | |
| Alternarienonic acid (247) | Alternaria sp. | [79,84] | |
| Talaroflavone (248) | Alternaria sp. | [84] | |
| Curvularin (249) | A. cinerariae | [126] | |
| A. tomato | [127] | ||
| (4S)-α,β-Dehydrocurvularin (250) | Alternaria sp. | [86] | |
| A. cinerariae | [126,128] | ||
| A. tenuissima | [86] | ||
| A. tomato | [127] | ||
| A. zinniae | [129] | ||
| β-Hydroxycurvularin (251) | A. tomato | [127] | |
| Resveratrol (252) | Alternaria sp. MG1 | [130] | |
| 6-(3',3'-dimethylallyloxy)-4-Methoxy-5-methylphthalide (253) | A. porri | [7] | |
| A. solani | [117] | ||
| A. tagetica | [116] | ||
| Porritoxinol (254) | A. porri | [131] | |
| 5-(3',3'-dimethylallyloxy)-7-Methoxy-6-methylphthalide (255) | A. porri | [7,32,34] | |
| A. solani | [118] | ||
| A. tagetica | [116] | ||
| Porriolide (256) | A. porri | [7,32] | |
| Miscellaneous Metabolites | Depudecin (257) | A. brassicicola | [132] |
| Altenin (258) | A. kikuchiana | [133] | |
| Brefeldin A (259) | A. carthami | [112] | |
| A. zinniae | [129] | ||
| 7-Dehydrobrefeldin A (260) | A. carthami | [112] | |
| α-Linoleic acid (261) | A. infectoria | [71] | |
| α-Linolenic acid (262) | A. infectoria | [71] | |
| AF-toxin I (263) | A. alternata | [134,135] | |
| AF-toxin II (264) | A. alternata | [134,135] | |
| AF-toxin III (265) | A. alternata | [134] | |
| Xanalteric acid I (266) | Alternaria sp. | [79] | |
| Xanalteric acid II (267) | Alternaria sp. | [79] | |
| Cladosporol (268) | A. alternate var. monosporus | [53] |
2.1. Nitrogen-Containing Metabolites
The nitrogen-containing compounds such as amides, amines, and cyclopeptides have been isolated from Alternaria fungi. Some of them belong to the host-selective phytotoxins in host-parasite interactions [39].
2.1.1. Amines and Amides
Amines and amides 1–33 are the common nitrogen-containing metabolites produced by Alternaria fungi (Figure 1). Ten sphinganine analogs designated AAL toxins 1–10 with an amino polyol backbone were isolated from A. alternata f.sp. lycopersici [16,17,18]. AAL toxins belong to host-specific phytotoxins. Very interestingly, AAL-toxins TB1 (3), TB2 (4), TC1 (5), TC2 (6), TD1 (7), TD2 (8), TE1 (9) and TE2 (10) have also been isolated from Fusarium moniliforme [136] and F. verticillioides [137]. Three amide alkaloids, AI-77-B (31), AI-77-F (32) and Sg17-1-4 (33), containing an isocoumarin structure were isolated from the marine fungus Alternaria tenuis Sg17-1 [42]. Other Alternaria amines and amides along with their distributions in Alternaria fungi are shown in Table 1.
Figure 1.
Amines and amides isolated from Alternaria fungi.
2.1.2. Cyclopeptides
Some Alternaria fungi can produce cyclopeptides 34–55 which are shown in Figure 2. Seven cyclopeptides, namely cyclo-(Pro-Ala-) (34), cyclo-(Pro-Pro-) (35), cyclo-[l-Leu-trans-4-hydroxy-L-Pro-] (37), cyclo-(S-Pro-R-Val-) (38), cyclo-(Pro-Leu-) (39), cyclo-(S-Pro-R-Ile-) (41), and cyclo-(Pro-Phe-) (42) were isolated from the endophytic fungus A. tenuissima derived from the bark of Erythrophleum fordii Oliver (Leguminosae) [22].
Three diketopiperazine dipeptides, namely cyclo-[l-Leu-trans-4-hydroxy-L-Pro-] (37), cyclo-(l-Phe-trans-4-hydroxy-l-Pro-) (44), and cyclo-(l-Ala-trans-4-hydroxy-L-Pro-) (45) were extracted from culture broth of the grapevine endophyte A. alternata [44].
Two cyclopeptides destruxins A (49) and B (50) were isolated from A. linicola [31]. Destruxin B (50) was also found in A. brassicae as the major phytotoxin [45]. Other cyclopeptides along with their distributions in Alternaria fungi are shown in Table 1.
Figure 2.
Cyclopeptides isolated from Alternaria fungi.
2.1.3. Other Nitrogen-Containing Metabolites
Other nitrogen-containing metabolites isolated from Alternaria fungi are shown in Figure 3. Two nucleosides namely uridine (56) and adenosine (57) were isolated from A. alternata [49].
Brassicicolin A (58), an isocyanide metabolite, was isolated as a mixture of epimers from A. brassicicola which was the pathogen of Brassica species [50,51]. Two indole alkaloids fumitremorgins B (59) and C (60) were produced by the endophytic fungus Alternaria sp. FL25 from Ficus carica (Moraceae) [52]. Paclitaxel (taxol, 61), a diterpenoid alkaloid with antitumor activity, was isolated from the endophytic fungus A. alternata var. monosporus obtained from the inner bark of Taxus yunnanensis (Taxaceae) [53]. Paclitaxel has also been isolated from yew trees (Taxus spp.) and their cell cultures [140,142].
Figure 3.
Other nitrogen-containing metabolites isolated from Alternaria fungi.
2.2. Steroids
Some steroids (62–68) have been isolated from Alternaria fungi (Figure 4 and Table 1). These findings are consistent with the considerations that ergosterol (62) and their derivatives are common to all fungi and occur widely among the fungi [143].
Figure 4.
Steroids isolated from Alternaria fungi.
2.3. Terpenoids
Most of terpenoids from Alternaria fungi have been found as the mixed terpenoids which have a multiple biogenesis (69–105). Other Alternaria terpenoids include diterpenoids 106–114, sesquiterpenoids 115,116 and a triterpenoid 117, which are shown in Figure 5.
Eleven bicycloalternarenes (BCAs, 69–79) were isolated and characterized from the culture filtrate of the phytopathogenic fungus A. alternata [56].
Nineteen tricycloalternarenes (TCAs) were isolated from the culture filtrate of the phytopathogenic fungus A. alternata from Brassica sinensis (Cruciferae). Tricycloalternarenes are closely related to ACTG toxins 87,88. Structural differences mainly occur in the isoprenoid side chain and the substitution pattern of the C-ring of the tricycloalternarenes [57,58,59,60].
Two tricycloalternarenes, ACTG toxins G (TCA 3b, 87) and H (88), along with a sesquiterpene (1aS,2S,6R,7R,7aR,7bR)-1a,2,4,5,6,7,7a,7b-octahydro-7,7a-dimethyl-1a-(1-methylethenyl)-naphth [1,2-b] oxirene-2,6-diol (116) were isolated from culture broth of A. citri, the pathogen causing brown spot disease of mandarin (Citrus reticulata) [61].
Nine fusicoccane diterpenes designated brassicicenes A-I 106–114 were isolated from the culture filtrate of the canola pathogen A. brassicicola [51,52,53,54,55,56,57,58,59,60,61,62].
Abscisic acid (ABA, 115), a sesquiterpenoid with plant growth regulation activity, was isolated from A. brassicae, a black spot pathogen of Brassica species (Cruciferae) [63].
Helvolic acid (117), a nortriterpenoid, was isolated from Alternaria sp. FL25, an endophytic fungus from Ficus carica (Moraceae) [43]. This metabolite (117) has also been isolated from Aspergillus fumigatus [138] and Pichia guilliermondii [139].
Figure 5.
Terpenoids isolated from Alternaria fungi.
2.4. Pyranones
Pyranones are also called pyrones which include α-, β- and γ-pyranones. Most of the pyranones isolated from Alternaria fungi belong to α-pyranones.
2.4.1. Simple Pyranones
The pyranones that do not contain benzene ring structure are defined as simple pyranones which belong to polyketides. Simple pyranones 118–149 from Alternaria fungi are shown in Figure 6. Three phytotoxins, ACRL toxins I (140), II (141) and III (142), with an α-dihydropyrone ring were isolated from A. citri, the causal agent of lemon (Citrus limon) [75,76].
Four metabolites namely novae-zelandins A (134) and B (135), 4Z-infectopyone (136), and infectopyrone (131) isolated from A. infectoria were thought to be important chemotaxonomic markers in the species group of A. infectoria [72].
Figure 6.
Simple pyranones isolated from Alternaria fungi.
2.4.2. Monobenzopyranones
Both benzo-α-pyranones and benzo-γ-pyranones have been found in Alternaria species (Figure 7 and Table 1). Benzo-α-pyranones are also called coumarin or isocoumarin derivatives. Four monobenzopyranones namely tenuissimassatin (150), altechromone A (151), 2,5-dimethyl-7-hydroxychromone (152) and phomapyrone F (153) were isolated from Alternaria fungi [22,55,79].
Figure 7.
Monobenzopyranones isolated from Alternaria fungi.
2.4.3. Dibenzopyranones
A few dibenzo-α-pyranones 154–166 have been found in Alternaria fungi so far. They are shown in Figure 8. Both alternariol (AOH, 157) and alternariol 9-methyl ether (AME, 159) represent the main toxic metabolites of Alternaria fungi.
Figure 8.
Dibenzopyranones isolated from Alternaria fungi.
2.4.4. Naphthopyranones
Seven naphtha-γ-pyranones 167–173 were found in A. alternata isolated from the marine soft coral Denderonephthya hemprichi (Figure 9). Among them, aurasperones A (170), B (171), C (172) and F (173) were dimeric naphtha-γ-pyranones [23].
Figure 9.
Naphthopyranones isolated from Alternaria fungi.
2.5. Quinones
Two groups of quinones, anthraquinone and perylenequine derivatives have been isolated in Alternaria fungi so far.
2.5.1. Anthraquinones
Figure 10 shows the structures of twenty-one simple anthraquinones 174–194 and twelve bianthraquinones 195–206 from Alternaria fungi. Nine tetrahydroanthraquinones 174–183, hydroxybostrycin (184) along with altersolanols A (185), B (186), C (187), D (188), E (189), F (190), G (191) and H (192) were isolated from A. solani, a causal pathogen of black spot disease on tomato (Lycopersicon esculentum) leaves [94,96].
Four bianthraquinones, alterporiols A/B (195), C (196), D/E (197), and F (198) were isolated from A. porri, the critical pathogen associated with the purple blotch disease of onion (Allium cepa) [32]. Three other bianthraquinones, alterporriols K (199), L (200) and M (201) were obtained from the mangrove endophytic fungus Alternaria sp. ZJ9-6B [100].
Figure 10.
Anthraquinones isolated from Alternaria fungi.
2.5.2. Perylenequinones
The perylenequinones are a class of metabolites characterized by a pentacyclic conjugated chromophore. Alternaria fungi produce a variety of partially reduced perylenequinone derivatives. A monochloridated perylenequinone namely 8β-chloro-3,6aα,7β,9β,10-pentahydroxy-9,8,7,6a-tetrahydroperylen-4(6aH)-one (208) along with alterperylenol (207) and dihydroalterperylenol (209) were isolated from a halotolerant fungus Alternaria sp. M6 obtained from the solar salt field at the beach of Bohai Bay in China [102]. Other perylenequinones 207–218 are shown in Figure 11.
Figure 11.
Perylenequinone derivatives isolated from Alternaria fungi.
2.6. Phenolics
The phenolic metabolites 219–256 from Alternaria fungi are shown in Figure 12, Figure 13. Most of them have a polyketide origin. One phenylpropanoid component was identified as methyl eugenol (223) by GC-MS from the volatile oil obtained by hydrodistillation from the Alternaria species isolated as the endophyte of rose (Rosa damascaena) [111]. Methyl eugenol (223) has been used as a flavouring agent in jellies, baked goods, non-alcoholic beverages, chewing gum, candy, pudding, relish, and ice cream [144].
Zinniol (226) along with its two analogues, bis-7-O-8''.8-O-7''-zinniol (237) and bis-7-O-7''.8-O-8''-zinniol (238), were isolated from the culture filtrate of A. tagetica, which was the causal agent of early blight in marigold (Tagetes erecta) [121].
One Alternaria species MG1 as the endophytic fungus from Vitis vinifera L. cv. Merlot could produce resveratrol (3,5,4'-trihydroxystilbene, 252) [130]. Resveratrol has been known for preventing and slowing the occurrence of some human diseases, including cancer, cardiovascular disease, and ischemic injuries. It has also been shown that resveratrol (252) can enhance stress resistance and extend the lifespan of various organisms ranging from yeasts to vertebrates [145]. Resveratrol has been found in a variety of plant species such as Vitis vinifera, Polygonum cuspidatum, and Glycine max [141]. Endophytic Alternaria species for producing plant-derived resveratrol should be an important and novel resource with its potential application in pharmaceutical industry [146].
Figure 12.
Phenolic metabolites isolated from Alternaria fungi.
Phthalides are considered as a special group of phenolic compounds. Four phthalates 253–256 were isolated from Alternaria fungi that are shown in Figure 13, and their occurrences are shown in Table 1.
Figure 13.
Phthalides isolated from Alternaria fungi.
2.7. Miscellaneous Metabolites
The miscellaneous metabolites 257–268 isolated from Alternaria fungi are shown in Figure 14. Depudecin (257) was an eleven-carbon linear polyketide isolated from A. brassicicola [132]. Two carboxylic acids namely xanalteric acids I (266) and II (267) were isolated from the endophytic fungus Alternaria sp. from the mangrove plant Sonneratia alba (Sonneratiaceae) [79].
Figure 14.
Miscellaneous metabolites isolated from Alternaria fungi.
3. Biological Activities and Functions
Alternaria metabolites with diverse chemical properties have been clarified (Figure 1, Figure 2, Figure 3, Figure 4, Figure 5, Figure 6, Figure 7, Figure 8, Figure 9, Figure 10, Figure 11, Figure 12, Figure 13, Figure 14, Table 1). Some of them act as phytotoxins to plants or as mycototoxins to humans and animals. They have been examined to have a variety of biological activities and functions, which mainly include the effects on plants, cytotoxic and antimicrobial activities.
3.1. Effects on Plants
Plant pathogenic Alternaria species can affect cereals, vegetables and fruit crops in the field and during storage. Alternaria fungi contamination is responsible for some of the world’s most devastating plant diseases, causing serious reduction of crop yields and considerable economic losses. The metabolites from plant pathogenic fungi are usually toxic to plants and are called phytotoxins. They were further divided into host-specific and host non-specific toxins. The host-specific toxins (HSTs) are toxic only to host plants of the fungus that produces the toxin [6,13]. Another definition seems to be more acceptable that the host-specific toxins are toxic to plants that host the pathogen, but have lower phytotoxicity on non-host plants [147,148]. Most HSTs are considered to be pathogenicity factors, which the fungi producing them require to invade tissue and induce disease [149] All isolates of the pathogen that produce an HST are pathogenic to the specific host. All isolates that fail to produce HSTs lose pathogenicity to the host plants. Plants that are susceptible to the pathogen are sensitive to the toxin. Such correlations between HST production and pathogenicity in the pathogens, and between toxin sensitivity and disease susceptibility in plants provide persuasive evidence that HSTs can be responsible for host-specific infection and disease development. Johnson and coworkers revealed that the genes involved in HST synthesis such as the cyclopeptide synthetase gene, whose product catalyzed AM toxin production in A. alternata apple pathotype, might reside on a conditionally dispensable (CD) chromosome. The loss of the CD chromosome led to loss of both toxin production and pathogenicity without affecting fungal growth [150]. On the other hand, the exact roles of non-specific toxins in pathogenesis are largely unknown, but some are thought to contribute to the features of virulence, such as the symptom development and in planta pathogen propagation [6]. The virulence and host-specificity of these pathogens are based on production of the distinctive HSTs [13]. For Alternaria pathogens, there are now at least nine diseases caused by Alternaria species in which HSTs are responsible for fungal pathogenicity (Table 2). Most of Alternaria HSTs are nitrogen-containing metabolites.
| Phytotoxin name | Alternaria species | Host plant | Plant disease | Reference |
|---|---|---|---|---|
| AAL-toxins TA1 (1), TA2 (2), TB1 (3), TB2 (4), TC1 (5), TC2 (6), TD1 (7), TD2 (8), TE1 (9), TE2 (10) | A. alternata f.sp. lycopersici | Tomato (Solanum lycopersicum) | Stem canker disease of tomato | [16,17,18] |
| ACT-toxins I (23) and II (24) | A. citri (A. alternata) | Mandarins and tangerine (Citrus spp.) | Brown spot of tangerine | [37,38] |
| AK-toxins I (25) and II (26) | A. kikuchiana (A. alternata) | Japanese pear (Pyrus serotina) | Black spot disease | [39,135] |
| AS-I toxin (27) | A. alternata | Sunflower (Helianthus annuus) | Necrotic spots on sunflower leaves | [40] |
| Maculosin (43) | A. alternata | Spotted knapweed (Centaurea maculosa) | Black leaf blight | [10,26] |
| AM-toxins I (46), II (47) and III (48) | A.mali (A. alternata) | Apple (Malus pumila) | Alternaria blotch of apple | [39] |
| Destruxin A (49), Destruxin B (50), Homodestruxin B (51), Desmethyldestruxin B (52) | A. brassicae | Brassica juncea; Brassica napus; Brassica rapa | Alternaria blackspot disease of Brassica | [46,148] |
| ACRL toxins I (140), II (141), III (142), IV (143), IV’(144) | A. citri | Rough lemon (Citrus limon) | Brown spot disease of Citrus | [75,76] |
| AF-toxins I (263), II (264) and III (265) | A. alternata | Strawberry (Fragaria spp.) | Alternaria balck spot of strawberry | [134,135] |
Among the HSTs, AAL toxins from tomato stem canker pathogen (A. alternata f.sp. lycopercici) have received a special attention. They were toxic to all tissues of sensitive tomato cultivars at low concentrations and induced apoptosis in sensitive tomato plants [151], and were found to inhibit de novo sphingolipid (ceramide) biosynthesis in vitro. Therefore, AAL toxins are called sphinganine-analog mycotoxins (SAMs). It has been reported that the tomato Alternaria stem canker locus mediated resistance to SAMs-induced apoptosis [152].
Destruxins are another group of HSTs produced both in vitro and in planta by A. brassicae, the causal agent of Alternaria blackspot disease of rapeseed and canola [148]. These cyclodepsipeptides exhibited a wide variety of biological activities such as antitumor, antiviral, insecticidal, cytotoxic, immunosuppressant, and antiproliferative effects except their phytotoxicity [153].
Interactions between Alternaria species and cruciferous plants were studied in detail by the Pedras group [51]. Nectrophic phytopathogens such as A. alternata and A. brassicae are known to synthesize phytotoxins that damage plant tissues and facilitate colonization, while in response to pathogen attack crucifers biosynthesize phytoanticipins and phytoalexins. Phytoalexins are secondary metabolites produced de novo by plants in response to diverse forms of stress including microbial infection, UV irradiation, and heavy metal salts, whereas phytoanticipins are constitutive defenses whose concentrations can increase upon stress [154]. To the detriment of cruciferous plants, the phytopathogens can overcome phytoanticipins and phytoalexins by producing detoxifying enzymes. For example, the phytoalexin brassinin (269) was detoxified into 3-indolylmethanamine (270) and N''-acetyl-3-indolylmethanamine (271) by the pathogen A. brassicae (Figure 15) [51]. Very interestingly, cruciferous plants (i.e., Brasicca napus and Sinapis alba) can convert host-specific toxins destruxin B (50) and homodestruxin B (51) into less phytotoxic hydrodestruxin B (272) and hydroxyhomodestruxin B (273), respectively (Figure 16) [155,156].
Figure 15.
Detoxification pathway of the phytoalexin brassinin (269) by the pathogen A. brassicicola [51].
Figure 15.
Detoxification pathway of the phytoalexin brassinin (269) by the pathogen A. brassicicola [51].
Figure 16.
Detoxification pathway of the phytotoxins destruxin B (50) and homodestruxin B (51) by the hosts Brassica napus and Sinapis alba [155,156].
Host non-specific Alternaria phytotoxins can affect many plants regardless of whether they are a host or non-host of the pathogen [6,13]. Host non-specific nitrogen-containing phytotoxins include tenuazonic acid (15), porritoxin (21) and tentoxin (53). Tentoxin (53), a cyclic tetrapeptide from A. alternata, inhibited chloroplast development, which phenotypically manifests itself as chlorotic tissue [157]. Tentoxin (53) was suggested to exert its effect on chlorophyll accumulation through overenergization of thylakoids [158]. Tenuazonic acid (TeA, 15) was investigated in Chlamydomonas reinhardtii thylakoids which revealed that TeA inhibited photophosphorylation with the action site at QB level [159].
Host non-specific pyranone phytotoxins include radicinin (118), deoxyradicinin (119), alternaric acid (133), alternuisol (154), altertenuol (155), dehydroaltenusin (156), alternariol (AOH, 157), alternariol 9-methyl ether (AME, 159), and alternuene (162). They are very common non-specific phytotoxic metabolites of Alternaria species [64,65,66,67,68,69,74,80,81,82,83,84,85].
Host non-specific quinone phytotoxins included bostrycin (182), 4-dexoybostrycin (183), and altersolanols A (185), B (186) and C (187) [93,94,95]. Altersolanol A (185), a tetrahydroanthraquinone phytotoxin from the culture broth of A. solani, inhibited the growth of cultured cells of Nicotiana rustica. It acted as a potent stimulator of NANH oxidation in the mitochondria isolated from N. rustica cells. Altersolanols acted as electron acceptors in an enzyme preparation of diaphorase. The capacity of altersolanols A, B, C, D, E and F to act as electron acceptors was in the order of A > E > C > B > F > D [160].
Host non-specific phenolic phytotoxins include zinniol (226) and its analogues 227–237. Zinniol (226) from the liquid cultures of A. tagetica induced leaf tissue necrosis in a number of unrelated plant species (Avena sativa, Cucumis sativus, Daucu carota, Hordeum vulgare, Triticum aestivum) from different families which demonstrated that zinniol acted as a non host-specific phytotoxin [161]. However, Qui et al. evaluated the effects of zinniol at the cellular level and showed that pure zinniol was not obviously phytotoxic at concentrations known to induce necrosis in leaves of Tagetes erecta, which indicated that the classification of zinniol as a host non-specific phytotoxin should be further investigated [162].
Other host non-specific phytotoxins include α,β-dehydrocurvularin (250) and brefeldin A (259) from A. zinniae. They showed phytotoxic activity on Xanthium occidentale, a widespread noxious weed of Australian summer crops and pastures. The fungus A. zinniae and its toxins may be used as the mycoherbicides in integrated weed management programs [129].
Some fungal phytotoxins were toxic to weed species to show their herbicidal potentials in agriculture and forestry [10,163,164,165]. Some examples are shown in Table 3. Weed pathogens should be a very promising source of bioactive natural products for weed control. Tentoxin (53) was transformed to isotentoxin (54) by UV irradiation. Isotentoxin (54) had stronger wilting effects than tentoxin against the weed Galium aparine [11].
| Phytotoxin name | Alternaria species | Target weed species | Reference |
|---|---|---|---|
| AAL-toxins ( 1–10) | A. alternata | Jimson weed ( Datura stramonium) | [166] |
| Tenuazonic acid ( 15) | A. alternata | Lantana camara | [12] |
| Maculosin ( 43) | A. alternata | Spotted knapweed ( Centaurea maculosa) | [10] |
| Tentoxin ( 53) | A. alternata | Galium aparine | [11] |
| Isotentoxin ( 54) | A. alternata | Galium aparine | [11] |
| Alteichin ( 213) | A. eichorniae | Water hyacinth ( Eichhornia crassipes) | [108] |
| Alternethanoxin A ( 245) | A. sonchi | Sonchus arvensis | [125] |
| Alternethanoxin B ( 246) | A.sonchi | Sonchus arvensis | [125] |
| Brefeldin A ( 259) | A. zinniae | Xanthium occidentale | [129] |
3.2. Cytotoxic Activity
Some Alternaria metabolites have been screened to show cytotoxic activity. They were thought as the potential sources for possible cancer chemopreventive agents. Porritoxin (21) was examined to have anti-tumor-promoting activity [7]. Three amides, AI-77-B (31), AI-77-F (32) and Sg17-1-4 (33), from a marine fungus A. tenuis Sg17-1 exhibited cytotoxic activity. Al-77-B (31) exhibited the cytotoxic activity on human malignant A375-S2 and human cervical cancer Hela cells with IC50 values of 0.1 and 0.02 mM, respectively. AI-77-F (32) showed a weak activity to Hela cells with an IC50 value of 0.4 mM. Sg17-1-4 (33) showed moderate activity with IC50 values of 0.3 and 0.05 mM, on malignant A375-S2 and Hela cells, respectively [42].
Of Alternaria dibenzopyranones, alternariol (157) was the most active metabolite to have cytotoxic activity on L5178Y mouse lymphoma cells [84], as well as to have inhibitory activity on protein kinase and xanthine oxidase [55]. Further investigation showed that alternariol (157) has been identified as a topoisomerase I and II poison which might contribute to the impairment of DNA integrity in human colon carcinoma cells [167]. It induced cell death by activation of the mitochondrial pathway of apoptosis in human colon carcinoma cells [168]. Alternariol and its 9-methyl ether induced cytochrome P450 1A1 and apoptosis in murine heptatoma cells dependent on the aryl hydrocarbon receptor [169]. Other alternariol derivatives such as alternariol 5-O-sulfate (158), alternariol 9-methyl ether (159), 3'-hydroxyalternariol (161), altenuene (162), 4'-epialtenuene (164) and dehydroaltenusin (156) were also screened to be cytotoxic [84]. Dehydroaltenusin (156), isolated from A. tenuis, was found to be a specific inhibitor of eukaryotic DNA polymerase α to show its strong cytotoxic activity on tumor cells [83,170].
Some screened Alternaria anthraquinones displayed cytotoxic activity. Demethylmacrosporin (175) was cytotoxic to Hela and KB cells with IC50 values of 7.3 μg/mL and 8.6 μg/mL, respectively [32]. Altersolanol C (187) was also screened to show cytotoxic activity on a few tumor cells [90]. A few bianthraquinones including alterporriols A/B (195), C (196), D/E (197), F (198), K (199), L (200), and P (204) showed strong cytotoxic activity on a few tumor cells [32,90,100,171]. Alterporriol L (200), a bianthraquinone derivative isolated from a marine fungus Alternaria sp. ZJ9-6B, inhibited the growth and proliferation of the MDA-MB-435 breast cancer cells through destroying the mitochondria [171].
Some Alternaria phenolic metabolites also have cytotoxic activity. Alterlactone (244) from Alternaria sp. was toxic on L5178Y mouse lymphoma cells [84]. Alternethanoxins A (245) and B (246) from A. sonchi displayed growth inhibitory activity on six cancer cell lines [172]. Both 6-(3',3'-dimethylallyloxy)-4-methoxy-5-methylphthalide (253) and 5-(3',3'-dimethylallyloxy)-7-methoxy-6-methylphthalide (255) were proved to have anti-tumor promoting activity [7]. 5-(3',3'-dimethylallyloxy)-7-methoxy-6-methylphthalide (255) had the cytotoxicity on Hela cells and KB cells with IC50 values as 36.0 μg/mL and 14.0 μg/mL, respectively. Porriolide (256) had the cytotoxicity on KB cells with IC50 value as 59.0 μg/mL [32]. Depudecin (257), an eleven-carbon linear polyketide from A. brassicicola, is an inhibitor of histone deacetylase (HDAC) to show its potential in cancer therapy [9].
3.3. Antimicrobial Activity
Three diketopiperazine dipeptides namely cyclo-[l-Leu-trans-4-hydroxy-L-Pro-] (37), cyclo-(l-Phe-trans-4-hydroxy-l-Pro-) (44), and cyclo-(l-Ala-trans-4-hydroxy-l-Pro) (45) extracted from broth culture of the grapevine endophyte A. alternata showed effectiveness by inhibiting sporulation of the pathogen Plasmopara viticola at concentrations of 10−3, 10−4, 10−5 and 10−6 mol/L. This indicated that endophytic fungus A. alternata can be used as biocontrol agent to control fungal disease in grapevine cultivation [44]. Cyclo-(Phe-Ser-) (36) from Alternaria sp. FL25 showed antifungal activity on Fusarium graminearum, F. oxysporum f.sp. cucumernum, F. oxysporum f.sp. neverum, Phytophthora capsici, Colletotrichum gloesporioides with MICs from 6.25 to 25.00 μg/mL [43]. Tenuazonic acid (15) was found to be an active compound in A. alternata against Mycobacterium tuberculosis H37Rv with MIC value of 250 μg/mL. This compound was thought as a promising antitubercular principle [28]. Other nitrogen-containing metabolites with antimicrobial activity included altersetin (12), pyrophen (14), tenuazonic acid (15) and brassicicolin A (58) [21,23,28,50,51,159].
Helvolic acid (117) from Alternaria sp. FL25, an endophytic fungus in Ficus carica, showed the strong antifungal activity on all tested phytopathogenic fungi (Alternaria alternata, A. brassicae, Botrytis cinerea, Colletotrichum gloesporioides, Fusarium graminearum, F. oxysporum, F. oxysporum f.sp. fragariae, F. oxysporum f.sp. niveum, Phytophthora capsici, Valsa mali) with MICs of 1.56–12.50 μg/mL [43].
Herbarin A (132) and altechromone A (151) from A. brassicicola ML-P08 exhibited antimicrobial activity on Trichophyton rubrum, Candida albicans, Apergillus niger, Bacillus subtilis, Escherichia coli, Pseudomonas fluorescens with MICs ranged from 1.8 to 62.5 μg/mL [55]. Rubrofusarin B (167) from A. alternata showed antifungal activity on Candida albicans [23].
Some anthraquinone metabolites, e.g., macrosporin (174), hydroxybostrycin (184), altersolanol A (185), altersolanol B (186), altersolanol C (187), altersolanol G (191), and alterporriol C (196) from A. solani and Alternaria sp. showed antibacterial activity on Bacillus subtilis, Escherichia coli, Micrococcus luteus, Pseudomonas aeruginosa, Staphylococcus albus, Staphylococcus aureus, Vibrio parahemolyticus [90,94,97]. Two perylenequnones alterperylenol (207) and dihydroalterperylenol (209) from Alternaria sp. had antifungal activity on Valsa ceratosperma [101].
Altenusin (241) and porric acid D (243) from Alternaria sp. showed inhibitory activity against Staphyloccus aureus with MICs of 100 μg/mL and 25 μg/mL, respectively [123]. (4S)-α,β-Dehydrocurvularin (250) from Alternaria sp. showed inhibitory activity on appressorium formation of Magnaporthe oryzae [86], and antibacterial activity on Proteus vulgaris and Salmonella typhimurium with MICs as 25 μg/mL [129].
3.4. Other Bioactivities
Altenusin (241) isolated from the endophytic fungus Alternaria sp. (UFMGCB55) in Trixis vauthieri (Compositae) was screened to show inhibitory activity on trypanothione reductase (TR), which is an enzyme involved in the protection of the parasitic Trypanosoma and Leishmania species against oxidative stress, and has been considered to be a validated drug target. Altenusin (241) had an IC50 value of 4.3 μM in the TR assay [122].
The association of mycotoxins from Alternaria fungi with human and animal health is not a recent phenomenon. Alternaria toxins have been linked to a variety of adverse effects (i.e., genotoxic, mutagenic, and carcinogenic) on human and animal health [173]. Tenuazonic acid (15) has been studied in detail for its toxicity to several animal species, e.g., mice, chickens, dogs. In dogs, it caused haemorrhages in several organs at daily doses of 10 mg/kg, and in chickens, sub-acute toxicity was observed with 10 mg/kg in the feed. In particular, increasing tenuazonic acid in chicken feed from sublethal to lethal levels progressively reduced feed efficiency, suppressed weight gain and increased internal haemorrhaging. Tenuazonc acid (15) is more toxic than AOH (157), AME (159) and ALT (162) [25,167]
There were a few reports about the toxicity of Alternaria metabolites on brine shrimp (Artemia salina L.) [23,107,174,175]. The LC50 values of tenuazonic acid (15), alternariol (157), altenuene (162) and altertoxin-I (212) were 75, 100, 375 and 200 μg/mL, respectively, to brine shrimp larvae by using the disk method of inoculation and an exposure period of 18 h [175]. Tenuazonic acid (15), alternariol (157), alternariol 9-methyl ether (159), altenuene (162), altertoxin I (212) were also verified to toxic to brine shrimp by other investigators [27,174,175]. Six naphthopyranones, namely rubrofusarin B (167), fonsecin (168), aurasperone A (170), aurasperone B (171), aurasperone C (172) and aurasperone F (173) from the marine-derived fungal strain A. alternata were screened to show inhibitory activity on brine shrimp (Artemia salina L.) at 10 μg/mL [23].
4. Conclusions and Future Perspectives
We just clarified one part of metabolites from the known Alternaria fungi. The rest of metabolties in Alternaria species need to be investigated in detail. In fact, many other Alternaria species remain unexplored for their metabolites. In most cases, both the biological activities and modes of action of the metabolites from Alternaria fungi have been studied very primarily. The structure-activity relationship has been established only for a few classes of Alternaria metabolites. This review mainly focused on the metabolites with low molecular weight from Alternaria fungi. Bioactive proteins, saccharides and glycoproteins are also important metabolites. Typical examples included a lipase from A. brassicicola [176], an endopolygalacturonase from the rough lemon pathotype of A. alternata [177], a protein elicitor (Hrip1) from A. tenuissima [178], and a polyketide synthase from A. alternata [179]. Some bioactive saccharides and glycoproteins have also been isolated such as β-1,3-, 1,6-oligoglucan elicitor from A. alternata [180] and a glycoprotein elicitor from A. tenuissima [181].
The potential applications of Alternaria metabolites as antitumor agents, herbicides, and antimicrobials as well as other promising bioactivities have led to considerable interest within the pharmaceutical community. Chemical syntheses have been achieved for a few bioactive metabolites such as AAL-toxin TA1 (1) [182], maculosin (43) [183], AM-toxin I (46) [184], alternariol (157) [185], alternariol 9-methyl ether (159) [185], altenuene (162) [186], isoaltenuene (163) [186], neoaltenuene (166) [187], altertoxin III (218) [188], zinniol (226) [189], altenusin (241) [190] and alterlactone (244) [190].
In recent years, more and more Alternaria fungi have been isolated as plant endophytic fungi from which large amounts of bioactive compounds have been structurally characterized. Another approach is to discovery novel bioactive compounds from the Alternaria fungi isolated from marine organisms. These Alternaria fungi could be the rich sources of biologically active compounds that are indispensable for medicinal and agricultural applications [191].
After comprehensive understanding of biosynthetic pathways of some Alternaria metabolites in the next few years, we can effectively not only increase yields of the bioactive metabolites, but also prohibit biosynthesis of some toxic metabolites (i.e., phytotoxins and mycotoxins) by treatment with some special fungicides.
Acknowledgments
This work was co-financed by the grants from the Hi-Tech R&D Program of China (2011AA10A202), the program for Changjiang Scholars and Innovative Research Team in University of China (IRT1042), and the National Natural Science Foundation of China (31271996).
Conflicts of Interest
The authors declare no conflict of interest.
References
- Thomma, B.P.H.J. Alternaria spp.: From general saprophyte to specific parasite. Mol. Plant Pathol. 2003, 4, 225–236. [Google Scholar] [CrossRef]
- Strange, R.N. Phytotoxins produced by plant pathogens. Nat. Prod. Rep. 2007, 24, 127–144. [Google Scholar] [CrossRef]
- Mobius, N.; Hertweck, C. Fungal phytotoxins as mediators of virulence. Curr. Opin. Plant Biol. 2009, 12, 390–398. [Google Scholar] [CrossRef]
- Duke, S.O.; Dayan, F.E. Modes of action of microbially-produced phytotoxins. Toxins 2011, 3, 1038–1064. [Google Scholar] [CrossRef]
- Brase, S.; Encinas, A.; Keck, J.; Nising, C.F. Chemistry and biology of mycotoxins and related fungal metabolites. Chem. Rev. 2009, 109, 3903–3990. [Google Scholar]
- Tsuge, T.; Harimoto, Y.; Akimitsu, K.; Ohtani, K.; Kodama, M.; Akagi, Y.; Egusa, M.; Yamamoto, M.; Otani, H. Host-selective toxins produced by the plant pathogenic fungus Alternaria alternata. FEMS Microbiol. Rev. 2013, 37, 44–66. [Google Scholar] [CrossRef]
- Horiuchi, M.; Tokuda, H.; Ohnishi, K.; Yamashita, M.; Nishino, H.; Maoka, T. Porritoxins, metabolites of Alternaria porri, as anti-tumor-promoting active compounds. Nat. Prod. Res. 2006, 20, 161–166. [Google Scholar]
- Monneret, C. Histone deacetylase inhibitors. Eur. J. Med. Chem. 2005, 40, 1–13. [Google Scholar] [CrossRef]
- Lakshmi, A.I.; Madhusudhan, T.; Kumar, P.D.; Padmavathy, J.; saravanan, D.; Kumar, P.C. Histone deacetylase inhibitors in cancer therapy: an update. Int. J. Pharm. Sci. Rev. Res. 2011, 10, 38–44. [Google Scholar]
- Stierle, A.C.; Cardellina II, J.H.; Strobel, G.A. Maculosin, a host-specific phytotoxin for spotted knapweed from Alternaria alternata. Proc. Natl. Acad. Sci. USA 1988, 85, 8008–8011. [Google Scholar] [CrossRef]
- Liebermann, B.; Ellinger, R.; Pinet, E. Isotentoxin, a conversion product of the phytotoxin tentoxin. Phytochemistry 1996, 42, 1537–1540. [Google Scholar]
- Sanodiya, B.S.; Thakur, G.S.; Baghel, R.K.; Pandey, A.K.; Bhogendra, G.; Prasad, K.S.; Bisen, P.S. Isolation and characterization of tenuazonic acid produced by Alternaria alternata, a potential bioherbicidal agent for control Lantana camara. J. Plant Prot. Res. 2010, 50, 133–139. [Google Scholar]
- Montemurro, N.; Visconti, A. Alternaria metabolites—Chemical and biological data. In Alternaria: Biology, Plant Disease and Metabolites; Chelkowski, J., Visconti, A., Eds.; Elsevier: Amsterdam, The Netherlands, 1992; pp. 449–557. [Google Scholar]
- Nishimura, S.; Kohmoto, K. Host-specific toxins and chemical structures from Alternaria species. Ann. Rev. Phytopathol. 1983, 21, 87–116. [Google Scholar] [CrossRef]
- Logrieco, A.; Moretti, A.; Solfrizzo, M. Alternaria toxins and plant diseases: and overview of origin, occurrence and risks. World Mycotoxin J. 2009, 2, 129–140. [Google Scholar] [CrossRef]
- Bottini, A.T.; Gilchrist, D.G. Phytotoxins. I. A 1-aminodimethylheptadecapentol from Alternaria alternata f.sp. lycopersici. Tetrahedron Lett. 1981, 22, 2719–2722. [Google Scholar] [CrossRef]
- Bottini, A.T.; Bowen, J.R.; Gilchrist, D.G. Phytotoxins. II. Characterization of a phytotoxic fraction from Alternaria alternata f.sp. lycopersici. Tetrahedron Lett. 1981, 22, 2723–2726. [Google Scholar] [CrossRef]
- Caldas, E.D.; Jones, A.D.; Ward, B.; Winter, C.K.; Gilchrist, D.G. Structural characterization of three new AAL toxins produced by Alternaria alternata f.sp. lycopersici. J. Agric. Food Chem. 1994, 42, 327–333. [Google Scholar]
- Abbas, H.K.; Riley, R.T. The presence and phytotoxicity of fumonisins and AAL-toxin in Alternaria alternata. Toxicon 1996, 34, 133–136. [Google Scholar] [CrossRef]
- Chen, J.; Mirocha, C.J.; Xie, W.; Hogge, L.; Olson, D. Production of the mycotoxin fumonisin B1 by Alternaria alternata f.sp. lycopersici. Appl. Environ. Microbiol. 1992, 58, 3928–3931. [Google Scholar]
- Hellwig, V.; Grothe, T.; Mayer-Bartschmid, A.; Endermann, R.; Geschke, F.-U.; Henkel, T.; Stadler, M. Altersetin, a new antibiotic from cultures of endophytic Alternaria spp. taxonomy, Fermentation, Isolation, Structure elucidation and biological activities. J. Antibiot. 2002, 55, 881–892. [Google Scholar]
- Fang, Z.F.; Yu, S.S.; Zhou, W.Q.; Chen, X.G.; Ma, S.G.; Li, Y.; Qu, J. A new isocoumarin from metabolites of the endophytic fungus Alternaria tenuissima (Nee & T. Nee: Fr) Wiltshire. Chin. Chem. Lett. 2012, 23, 317–320. [Google Scholar]
- Shaaban, M.; Shaaban, K.A.; Abdel-Aziz, M.S. Seven naphtho-γ-pyrones from the marine-derived fungus Alternaria alternata: Structure elucidation and biological properties. Org. Med. Chem. Lett. 2012, 2, 6. [Google Scholar]
- Davis, N.D.; Diener, U.L.; Morgan-Jones, G. Tenuazonic acid production by Alternaria alternata and Alternaria tenuissima isolated from cotton. Appl. Environ. Microbiol. 1977, 34, 155–157. [Google Scholar]
- Griffin, G.F.; Chu, F.S. Toxicity of the Alternaria metabolites alternariol, Alternariol methyl ether, Altenuene, and tenuazonic acid in the chicken embryo assay. Appl. Environ. Microbiol. 1983, 46, 1420–1422. [Google Scholar]
- Stierle, A.C.; Cardellina II, J.H.; Strobel, G.A. Phytotoxins from Alternaria alternata, a pathogen of spotted knapweed. J. Nat. Prod. 1989, 52, 42–47. [Google Scholar]
- Qin, J.-C.; Zhang, Y.-M.; Hu, L.; Ma, Y.-T.; Gao, J.-M. Cytotoxic metabolites produced by Alternaria no.28, an endophytic fungus isolated from Ginkgo biloba. Nat. Prod. Commun. 2009, 4, 1473–1476. [Google Scholar]
- Sonaimuthu, V.; Parihar, S.; Thakur, J.P.; Luqman, S.; Saikia, D.; Chanotiya, C.S.; Jhonpaul, M.; Negi, A.S. Tenuazonic acid: A promising antitubercular principle from Alternaria alternata. Microbiol. Res. 2010, 2, 63–65. [Google Scholar]
- Kono, Y.; Gardner, J.M.; Takeuchi, S. Nonselective phytotoxins simultaneously produced with host-selective ACTG-toxins by a pathotype of Alternaria citri causing brown spot disease of mandarins. Agric. Biol. Chem. 1986, 50, 2401–2403. [Google Scholar]
- Sattar, A.; Alam, M.; Janardhanan, K.K.; Husain, A. Isolation of tenuazonic acid, a phytotoxin from Alternaria crassa (Sacc.) rands causing leaf blight and fruit rot of Datura stramonium Mill. Curr. Sci. 1986, 55, 195–196. [Google Scholar]
- Evans, N.; Mcroberts, N.; Hill, R.A.; Marshall, G. Phytotoxin production by Alternaria linicola and phytoalexin production by the linseed host. Ann. Appl. Biol. 1996, 129, 415–431. [Google Scholar] [CrossRef]
- Phuwapraisirisan, P.; Rangsan, J.; Siripong, P.; Tip-pyang, S. New antitumour fungal metabolites from Alternaria porri. Nat. Prod. Res. 2009, 23, 1063–1071. [Google Scholar] [CrossRef]
- Stierle, A.; Hershenhorn, J.; Strobel, G. Zinniol-related phytotoxins from Alternaria cichorii. Phytochemistry 1993, 32, 1145–1149. [Google Scholar]
- Suemitsu, R.; Ohnishi, K.; Morikawa, Y.; Nagatomo, S. Zinnimidine and 5-(3’,3’-dimethylallyloxy)-7-methoxy-6-methylphthalide from Alternaria porri. Phytochemistry 1995, 38, 495–497. [Google Scholar]
- Horiuchi, M.; Ohnishi, K.; Iwase, N.; Nakajima, Y.; Tounai, K.; Yamashita, M.; Yamada, Y. A novel isoindoline, porritoxin sulfonic acid, from Alternaria porri and the structure-phytotoxicity correlation of its related compounds. Biosci. Biotechnol. Biochem. 2003, 67, 1580–1583. [Google Scholar]
- Horiuchi, M.; Maoka, T.; Iwase, N.; Ohnishi, K. Reinvestigation of structure of porritoxin, a phytotoxin of Alternaria porri. J. Nat. Prod. 2002, 65, 1204–1205. [Google Scholar] [CrossRef]
- Kohmoto, K.; Itoh, Y.; Shimomura, N.; Kondoh, Y.; Otani, H.; Kodama, M.; Nishimura, S.; Nakatsuka, S. Isolation and biological activities of two host-specific toxins from the tangerine pathotype of Alternaria alternata. Phytopathology 1993, 83, 495–502. [Google Scholar] [CrossRef]
- Masunaka, A.; Ohtani, K.; Peever, T.L.; Timmer, L.W.; Tsuge, T.; Yamamoto, M.; Yamamoto, H.; Akimitsu, K. An isolate of Alternaria alternata that is pathogenic to both tangerines and rough lemon and produces two host-selective toxins, ACT- and ACR-toxins. Phytopathology 2005, 95, 241–247. [Google Scholar] [CrossRef]
- Ueno, T. Secondary metabolites related to host selection by plant pathogenic fungi. Pure Appl. Chem. 1990, 62, 1347–1352. [Google Scholar] [CrossRef]
- Liakopoulou-Kyriakides, M.; Lagopodi, A.L.; Thanassoulopoulos, C.C.; Stavropoulos, G.S.; Magafa, V. Isolation and synthesis of a host-selective toxin produced by Alternaria alternata. Phytochemistry 1997, 45, 37–40. [Google Scholar]
- Wu, S.; Chen, Y.; Li, Z.; Yang, L.; Li, S. Metabolites of the endophytic fungus Alternaria sp. PR-14 of Paeonia delavayi. Nat. Prod. Res. Dev. 2011, 23, 850–852. [Google Scholar]
- Huang, Y.-F.; Li, L.-H.; Tian, L.; Qiao, L.; Hua, H.-M.; Pei, Y.-H. Sg17–1-4, a novel isocoumarin from a marine fungus Alternaria tenuis Sg17–1. J. Antibiot. 2006, 59, 355–357. [Google Scholar] [CrossRef]
- Feng, C.; Ma, Y. Isolation and anti-phytopathogenic activity of secondary metabolites from Alternaria sp. FL25, an endophytic fungus in Ficus carica. Chin. J. Appl. Environ. Biol. 2010, 16, 76–78. [Google Scholar] [CrossRef]
- Musetti, R.; Polizzotto, R.; Vecchione, A.; Borselli, S.; Zulini, L.; D’Ambrosio, M.; Di Toppi, L.S.; Pertot, I. Antifungal activity of diketopiperazines extracted from Alternaria alternata against Plasmopara viticola: an ultrastructural study. Micron 2007, 38, 643–650. [Google Scholar]
- Buchwaldt, L.; Green, H. Phytotoxicity of destruxin B and its possible role in the pathogenesis of Alternaria brassicae. Plant Pathol. 1992, 41, 55–63. [Google Scholar] [CrossRef]
- Ayer, W.A.; Pena-Rodriguez, L.M. Metabolites produced by Alternaria brassicae, the black spot pathogen of canola. Part 1, the phytotoxic components. J. Nat. Prod. 1987, 50, 400–407. [Google Scholar] [CrossRef]
- Liebermann, B.; Koelblin, R. A new phytotoxic activity of the cyclic peptides tentoxin and dihydrotentoxin. J. Phytopathol. 1992, 135, 245–250. [Google Scholar] [CrossRef]
- Horiuchi, M.; Akimoto, N.; Ohnishi, K.; Yamashita, M.; Maoka, T. Rapid and simultaneous determination of tetra cyclic peptide phytotoxins, tentoxin, isotentoxin and dihydrotentoxin, from Alternaria porri by LC/MS. Chromatography 2003, 24, 109–116. [Google Scholar]
- Ma, Y.-T.; Qiao, L.-R.; Shi, W.-Q.; Zhang, A.-L.; Gao, J.-M. Metabolites produced by an endophyte Alternaria alternata isolated from Maytenus hookeri. Chem. Nat. Compd. 2010, 46, 504–506. [Google Scholar] [CrossRef]
- Gloer, J.B.; Poch, G.K.; Short, D.M.; McCloskey, D.V. Structure of brassicicolin A: A novel isocyanide antibiotic from the phylloplane fungus Alternaria brassicicola. J. Org. Chem. 1988, 53, 3758–3761. [Google Scholar]
- Pedras, M.S.C.; Chumala, P.B.; Jin, W.; Islam, M.S.; Hauck, D.W. The phytopathogenic fungus Alternaria brassicicola: Phytotoxin production and phytoalexin elicitation. Phytochemistry 2009, 70, 394–402. [Google Scholar]
- Ma, Y.; Feng, C.; Zhang, H.; Zhou, X. Two indole alkaloids produced by endophytic fungus FL25 from Ficus carica. Chem. Res. Appl. 2009, 21, 1173–1175. [Google Scholar]
- Chen, J.; Qiu, X.; Wang, R.; Duan, L.; Chen, S.; Luo, J.; Kong, L. Inhibition of human gastric carcinoma cell growth in vitro and in vivo by cladosporol isolated from the paclitaxel-producing strain Alternaria alternata var. monosporus. Biol. Pharm. Bull. 2009, 32, 2072–2074. [Google Scholar] [CrossRef]
- Seitz, L.M.; Paukstelis, J.V. Metabolites of Alternaria alternata: ergosterol and ergosta-4,6,8(14),22-tetraen-3-one. J. Agric. Food Chem. 1977, 25, 838–841. [Google Scholar] [CrossRef]
- Gu, W. Bioactive metabolites from Alternaria brassicicola ML-P08, an endophytic fungus residing in Malus halliana. World J. Microbiol. Biotechnol. 2009, 25, 1677–1683. [Google Scholar] [CrossRef]
- Liebermann, B.; Nussbaum, R.-P.; Gunther, W. Bicycloalternarenes produced by the phytopathogenic fungus Alternaria alternata. Phytochemistry 2000, 55, 987–992. [Google Scholar]
- Liebermann, B.; Ellinger, R.; Gunther, W.; Ihn, W.; Gallander, H. Tricycloalternarenes produced by Alternaria alternata related to ACTG-toxins. Phytochemistry 1997, 46, 297–303. [Google Scholar]
- Yuan, L.; Zhao, P.-J.; Ma, J.; Li, G.-H.; Shen, Y.-M. Tricycloalternarenes A-E: Five new mixed terpenoids from the endophytic fungal strain Alternaria alternata Ly83. Helv. Chim. Acta 2008, 91, 1588–1594. [Google Scholar] [CrossRef]
- Nussbaum, R.-P.; Gunther, W.; Heinze, S.; Liebermann, B. New tricycloalternarenes produced by the phytopathogenic fungus Alternaria alternata. Phytochemistry 1999, 52, 593–599. [Google Scholar]
- Qiao, L.-R.; Yuan, L.; Gao, J.-M.; Zhao, P.-J.; Kang, Q.-J.; Shen, Y.-M. Tricycloalternarene derivatives produced by an endophyte Alternaria alternata isolated from Maytenus hookeri. J. Basic Microbiol. 2007, 47, 340–343. [Google Scholar]
- Kono, Y.; Gardner, J.M.; Suzuki, Y.; Kondo, H.; Takeuchi, S. New minor components of host-selective ACTG-toxin and a novel sesquiterpene produced by a pathotype of Alternaria citri causing brown spot disease of mandarins. Nippon Noyaku Gakkaishi 1989, 14, 223–228. [Google Scholar]
- MacKinnon, S.L.; Keifer, P.; Ayer, W.A. Components from the phytotoxic extract of Alternaria brassicicola, a black spot pathogen of canola. Phytochemistry 1999, 51, 215–221. [Google Scholar]
- Dahiya, J.S.; Tewari, J.P.; Woods, D.L. Abscisic acid from Alternaria brassicae. Phytochemistry 1988, 27, 2983–2984. [Google Scholar] [CrossRef]
- Robeson, D.J.; Gray, G.R.; Strobel, G.A. Production of the phytotoxins radicinin and radicinol by Alternaria chrysanthemi. Phytochemitry 1982, 21, 2359–2362. [Google Scholar]
- Sheridan, H.; Canning, A.-M. Novel radicinol derivatives from long-term cultures of Alternaria chrysanthemi. J. Nat. Prod. 1999, 62, 1568–1569. [Google Scholar] [CrossRef]
- Tal, B.; Robeson, D.J.; Burke, B.A.; Aasen, A.J. Phytotoxins from Alternaria helianthi: radicinin and the structures of deoxyradicinol and radianthin. Phytochemistry 1985, 24, 729–731. [Google Scholar]
- Solfrizzo, M.; Vitti, C.; De Girolamo, A.; Visconti, A.; Logrieco, A.; Fanizzi, F.P. Radicinols and radicinin phytotoxins produced by Alternaria radicina on carrots. J. Agric. Food Chem. 2004, 52, 3655–3660. [Google Scholar] [CrossRef]
- Chen, Q.F.; Zhou, M.; Yang, T.; Chen, X.Z.; Wang, C.; Zhang, G.L.; Li, G.Y. Secondary metabolites from fungus Alternaria sp. CIB108. Chin. Chem. Lett. 2011, 22, 1226–1228. [Google Scholar]
- Robeson, D.J.; Strobel, R.A. Deoxyradicinin, a novel phytotoxin from Alternaria helianthi. Phytochemistry 1982, 21, 1821–1823. [Google Scholar]
- Robeson, D.J.; Strobel, G.A. Deoxyradicinin and 3-epideoxyradicinol production by the sunflower pathogen Alternaria helianthi. Ann. Appl. Biol. 1985, 107, 409–415. [Google Scholar] [CrossRef]
- Ivanova, L.; Petersen, D.; Uhlig, S. Phomenins and fatty acids from Alternaria infectoria. Toxicon 2010, 55, 1107–1114. [Google Scholar] [CrossRef]
- Christensen, K.B.; Van Klink, J.W.; Weavers, R.T.; Larsen, T.O.; Andersen, B.; Phipps, R.K. Novel chemotaxonomic markers of the Alternaria infectoria species-group. J. Agric. Food Chem. 2005, 53, 9431–9435. [Google Scholar]
- Larsen, T.O.; Perry, N.B.; Andersen, B. Infectopyrone, a potential mycotoxin from Alternaria infectoria. Tetrahedron Lett. 2003, 44, 4511–4513. [Google Scholar] [CrossRef]
- Patel, S.J.; Subramanian, R.B.; Jha, Y.S. A simple and rapid method for isolation of alternaric acid from Alternaria solani. Curr. Trends Biotechnol. Pharm. 2011, 5, 1098–1103. [Google Scholar]
- Gardner, J.M.; Kono, Y.; Tatum, J.H.; Suzuki, Y.; Takeuchi, S. Plant pathotoxins from Alternaria citri: the major toxin specific for rough lemon plants. Phytochemistry 1985, 24, 2861–2867. [Google Scholar] [CrossRef]
- Kono, Y.; Gardner, J.M.; Suzuki, Y.; Takeuchi, S. Plant pathotoxins from Alternaria citri: the minor ACRL toxins. Phytochemistry 1985, 24, 2869–2874. [Google Scholar] [CrossRef]
- Ichihara, A.; Tazaki, H.; Sakamura, S. Solanapyrones A, B and C, phytotoxic metabolites from the fungus Alternaria solan. Tetrahedron Lett. 1983, 24, 5373–5376. [Google Scholar] [CrossRef]
- Oikawa, H.; Yokota, T.; Sakano, C.; Suzuki, Y.; Naya, A.; Ichiara, A. Solanapyrones, phytotoxins produced by Alternaria solani: Biosynthesis and isolation of minor components. Biosci. Biotechnol. Biochem. 1988, 62, 2016–2022. [Google Scholar]
- Kjer, J.; Wray, V.; Edrada-Ebel, R.A.; Ebel, R.; Pretsch, A.; Lin, W.; Proksch, P. Xanalteric acids I and II and related phenolic compounds from an endophytic Alternaria sp. isolated from the mangrove plant Sonneratia alba. J. Nat. Prod. 2009, 72, 2053–2057. [Google Scholar] [CrossRef]
- Chu, F.S. Isolation of altenuisol and altertoxins I and II, minor mycotoxins elaborated by Alternaria. J. Am. Oil Chem. Soc. 1981, 58, 1006–1008. [Google Scholar] [CrossRef]
- Pero, R.W.; Harvan, D.; Blois, M.C. Isolation of the toxin, altenuisol, from the fungus, Alternaria tenuis Auct. Tetrahedron Lett. 1973, 12, 945–948. [Google Scholar] [CrossRef]
- Thomas, R. Biosyntesis of fungal metabolites. IV. Alternariol monomethyl ether and its relation to other phenolic metabolites of Alternaria tenuis. Biochem. J. 1961, 80, 234–240. [Google Scholar]
- Maeda, N.; Kokai, Y.; Ohtani, S.; Sahara, H.; Kuriyama, I.; Kamisuki, S.; Takahashi, S.; Sakaguchi, K.; Sugawara, F.; Yoshida, H. Anti-tumor effects of dehydroaltenusin, a specific inhibitor of mammalian DNA polymerase α. Biochem. Biophys. Res. Commun. 2007, 352, 390–396. [Google Scholar] [CrossRef]
- Aly, A.H.; Edrada-Ebel, R.; Indriani, I.D.; Wray, V.; Muller, W.E.G.; Totzke, F.; Zirrgiebel, U.; Schachtele, C.; Kubbutat, M.H.G.; Lin, W.H.; et al. Cytotoxic metabolites from the fungal endophyte Alternaria sp. and their subsequent detection in its host plant Polygonum senegalense. J. Nat. Prod. 2008, 71, 972–980. [Google Scholar] [CrossRef]
- Watanabe, I.; Kakishima, M.; Adachi, Y.; Nakajima, H. Potential mycotoxin productivity of Alternaria alternata isolated from garden trees. Mycotoxins 2007, 57, 3–9. [Google Scholar] [CrossRef]
- Jeon, Y.-T.; Ryu, K.-H.; Kang, M.-K.; Park, S.-H.; Yun, H.; QT, P.; Kim, S.-U. Alternariol monomethyl ether and α,β-dehydrocurvularin from endophytic fungi Alternaria spp. inhibit appressorium formation of Magnaporthe grisea. J. Korean Soc. Appl. Biol. Chem. 2010, 53, 39–42. [Google Scholar]
- Pero, R.W.; Main, C.E. Chlorosis of tobacco induced by alternariol monomethyl ether produced by Alternaria tenuis. Phytopathology 1970, 60, 1570–1573. [Google Scholar] [CrossRef]
- Visconti, A.; Bottalico, A.; Solfrizzo, M.; Palmisano, F. Isolation and structure elucidation of isoaltenuene, a new metabolite of Alternaria alternata. Mycotoxin Res. 1989, 5, 69–76. [Google Scholar] [CrossRef]
- Bradburn, N.; Coker, R.D.; Blunden, G.; Turner, C.H.; Crabb, T.A. 5'-Epialtenuene and neoaltenuene, dibenzo-α-pyrones from Alternaria alternata cultured on rice. Phytochemistry 1994, 35, 665–669. [Google Scholar]
- Zheng, C.-J.; Shao, C.-L.; Guo, Z.-Y.; Chen, J.-F.; Deng, D.-S.; Yang, K.-L.; Chen, Y.-Y.; Fu, X.-M.; She, Z.-G.; Lin, Y.-C.; et al. Bioactive hydroanthraquinones and anthraquinone dimers from a soft coral-derived Alternaria sp. fungus. J. Nat. Prod. 2012, 75, 189–197. [Google Scholar] [CrossRef]
- Stoessl, A.; Unwin, C.H.; Stothers, J.B. Metabolites of Alternaria solani. Part V. Biosynthesis of altersolanol A and incorporation of carbon-13 labeled altersolanol A into altersolanol B and macrosporin. Tetrahedron Lett. 1979, 27, 2481–2484. [Google Scholar] [CrossRef]
- Stoessl, A.; Stothers, J.B. Metabolites of Alternaria solani. Part VIII. Tetrahydroaltersolanol B, a hexahydroanthronol from Alternaria solani. Can. J. Chem. 1983, 61, 378–382. [Google Scholar] [CrossRef]
- Charudattan, R.; Rao, K.V. Bostrycin and 4-deoxybostrycin: Two nonspecific phytotoxins produced by Alternaria eichhorniae. Appl. Environ. Microbiol. 1982, 43, 846–849. [Google Scholar]
- Okamura, N.; Haraguchi, H.; Hashimoto, K.; Yagi, A. Altersolanol-related antimicrobial compounds from a strain of Alternaria solani. Phytochemistry 1993, 34, 1005–1009. [Google Scholar] [CrossRef]
- Suemitsu, R.; Yamada, Y.; Sano, T.; Yamashita, K. Studies of the metabolic products of Alternaria porri (Ellis) Ciferri. Part XII. Phytotoxic activities of altersolanol A, B and dactylariol, and activities of altersolanol A against some microorganisms. Agric. Biol. Chem. 1984, 48, 2383–2384. [Google Scholar] [CrossRef]
- Okamura, N.; Yagi, A.; Haraguchi, H.; Hashimoto, K. Simultaneous high-performance liquid chromatographic determination of altersolanol A, B, C, D, E and F. J. Chromatogr. 1992, 630, 418–422. [Google Scholar]
- Yagi, A.; Okamura, N.; Haraguchi, H.; Abo, T.; Hashimoto, K. Antimicrobial tetrahydroanthraquinones from a strain of Alternaria solani. Phytochemistry 1993, 33, 87–91. [Google Scholar]
- Suemitsu, R.; Nakamura, A.; Isono, F.; Sano, T. Studies on the metabolic products of Alternaria porri (Ellis) Ciferri. Part XI. Isolation and identification of dactylariol from the culture liquid Alternaria porri (Ellis) Ciferri. Agric. Biol. Chem. 1982, 46, 1693–1694. [Google Scholar] [CrossRef]
- Suemitsu, R.; Horiuchi, K.; Kubota, M.; Okamatsu, T. Production of alterporriols, altersolanols and marosporin by Alternaria porri and A. solani. Phytochemistry 1990, 29, 1509–1511. [Google Scholar]
- Huang, C.-H.; Pan, J.-H.; Chen, B.; Yu, M.; Huang, H.-B.; Zhu, X.; Lu, Y.-J.; She, Z.-G.; Lin, Y.-C. Three bianthraquinone derivatives from the mangrove endophytic fungus Alternaria sp. ZJ9–6B from the South China Sea. Mar. Drugs 2011, 9, 832–843. [Google Scholar] [CrossRef]
- Okuno, T.; Natsume, I.; Sawai, K.; Sawamura, K.; Furusaki, A.; Matsumoto, T. Structure of antifungal and phytotoxic pigments produced by Alternaria species. Tetrahedron Lett. 1983, 24, 5653–5656. [Google Scholar]
- Zhang, S.-Y.; Li, Z.-L.; Bai, J.; Wang, Y.; Zhang, L.-M.; Wu, X.; Hua, H.-M. A new perylenequinone from a halotolerant fungus, Alternaria sp. M6. Chin. J. Nat. Med. 2012, 10, 68–71. [Google Scholar] [CrossRef]
- Hradil, C.M.; Hallock, Y.F.; Clardy, J.; Kenfield, D.S.; Strobel, G. Phytotoxins from Alternaria cassiae. Phytochemistry 1989, 28, 73–75. [Google Scholar]
- Stack, M.E.; Mazzola, E.P.; Page, S.W.; Pohland, A.E.; Highet, R.J.; Tempesta, M.S.; Corley, D.G. Mutagenic perylenequinone metabolites of Alternaria alternata: altertoxins I, II and III. J. Nat. Prod. 1986, 49, 866–871. [Google Scholar] [CrossRef]
- Gao, S.-S.; Li, X.-M.; Wang, B.-G. Perylene derivatives produced by Alternaria alternata, an endophytic fungus isolated from Laurencia species. Nat. Prod. Commun. 2009, 4, 1477–1480. [Google Scholar]
- Hu, D.; Liu, M.; Xia, X.; Chen, D.; Zhao, F.; Ge, M. Preparative isolation and purification of altertoxin I from an Alternaria sp. by HSCCC. Chromatographia 2008, 67, 863–867. [Google Scholar] [CrossRef]
- Visconti, A.; Sibilia, A.; Sabia, C. Alternaria alternata from oilseed rape: mycotoxin production, and toxicity to Artemia salina larvae and rape seedlings. Mycotoxin Res. 1992, 8, 9–16. [Google Scholar] [CrossRef]
- Robeson, D.; Strobel, G.; Matusumoto, G.K.; Fisher, E.L.; Chen, M.H.; Clardy, J. Alteichin: An unusual phytotoxin from Alternaria eichorniae, a fungal pathogen of water hyacinth. Experientia 1984, 40, 1248–1250. [Google Scholar] [CrossRef]
- Gamboa-Angulo, M.M.; Garcia-Sosa, K.; Alejos-Gonzalez, F.; Escalante-Erosa, F.; Delgado-Lamas, G.; Pena-Rodriguez, L.M. Tagetolone and tagetenolone: two phytotoxic polyketides from Alternaria tagetica. J. Agric. Food Chem. 2001, 49, 1228–1232. [Google Scholar] [CrossRef]
- Xia, X.; Qi, J.; Wei, F.; Jia, A.; Yuan, W.; Meng, X.; Zhang, M.; Liu, C.; Wang, C. Isolation and characterization of a new benzofuran from the fungus Alternaria sp. (HS-3) associated with a sea cucumber. Nat. Prod. Commun. 2011, 6, 1913–1914. [Google Scholar]
- Kaul, S.; Wani, M.; Dhar, K.L.; Dhar, M.K. Production and GC-MS trace analysis of methyl eugenol form endophytic isolate of Alternaria from rose. Ann. Microbiol. 2008, 58, 443–445. [Google Scholar] [CrossRef]
- Tietjen, K.G.; Schaller, E.; Matern, U. Phytotoxins from Alternaria carthami Chowdhury: Structural identification and physiological significance. Physiol. Plant Pathol. 1983, 23, 387–400. [Google Scholar] [CrossRef]
- Cotty, P.J.; Misaghi, I.J. Zinniol production by Alternaria species. Phytopathology 1984, 74, 785–788. [Google Scholar] [CrossRef]
- Berestetskii, A.O.; Yuzikhin, O.S.; Katkova, A.S.; Dobrodumov, A.V.; Sivogrivov, D.E.; Kolombet, L.V. Isolation, Identification, and characteristics of the phytotoxin produced by the fungus Alternaria cirsinoxia. Appl. Biochem. Microbiol. 2010, 46, 75–79. [Google Scholar] [CrossRef]
- Barasch, I.; Mor, H.; Netzer, D.; Kashman, Y. Production of zinniol by Alternaria dauci and its phytotoxic effect on carrot. Physiol. Plant Pathol. 1981, 19, 7–16. [Google Scholar]
- Gamboa-Angulo, M.M.; Escalante-Erosa, F.; Garcia-Sosa, K.; Alejos-Gonzalez, F.; Delgado-Lamas, G.; Pena-Rodriguez, L.M. Natural zinniol derivatives from Alternaria tagetica. Isolation, synthesis, and structure-activity correlation. J. Agric. Food Chem. 2002, 50, 1053–1058. [Google Scholar] [CrossRef]
- Gamboa-Angulo, M.M.; Alejos-Gonzalez, F.; Pena-Rodriguez, L.M. Homozinniol, a new phytotoxic metabolite from Alternaria solani. J. Agric. Food Chem. 1997, 45, 282–285. [Google Scholar]
- Moreno-Escobar, J.; Puc-Carrillo, A.; Ceres-Farfan, M.C.A.; Pena-Rodriguez, L.M.; Gamboa-Angulo, M.M. Two new zinniol-related phytotoxins from Alternaria solani. Nat. Prod. Res. 2005, 19, 603–607. [Google Scholar] [CrossRef]
- Cotty, P.J.; Mishagi, I.; Hine, R. Produciton of zinniol by Alternaria tagetica and its phytotoxic effect on Tagetes erecta. Phytopathology 1983, 73, 1326–1328. [Google Scholar] [CrossRef]
- Starratt, A.N. Zinniol: a major metabolite of Alternaria zinniae. Can. J. Chem. 1968, 46, 767–770. [Google Scholar] [CrossRef]
- Gamboa-Angulo, M.M.; Alejos-Gonzalez, F.; Escalante-Erosa, F.; Garcia-Sosa, K.; Delgado-Lamas, G.; Pena-Rodriguez, L.M. Novel dimeric metabolites from Alternaria tagetica. J. Nat. Prod. 2000, 63, 1117–1120. [Google Scholar] [CrossRef]
- Cota, B.B.; Rosa, L.H.; Caligiorne, R.B.; Rabello, A.L.T.; Alves, T.M.A.; Rosa, C.A.; Zani, C.L. Altenusin, a biphenyl isolated from the endophytic fungus Alternaria sp., inhibits trypanothione reductase from Trypanosoma cruzi. FEMS Microbiol. Lett. 2008, 285, 177–182. [Google Scholar] [CrossRef]
- Xu, X.; Zhao, S.; Wei, J.; Fang, N.; Yin, L.; Sun, J. Porric acid D from marine-derived fungus Alternaria sp. isoltated from Bohai Sea. Chem. Nat. Compd. 2012, 47, 893–895. [Google Scholar] [CrossRef]
- Chadwick, D.J.; Easton, I.W.; Johnstone, R.A.W. Fungal metabolites. Part 9. Isolation and x-ray structure determination of alternarian acid from Alternaria mali Sp. Tetrahedron 1984, 40, 2451–2455. [Google Scholar] [CrossRef]
- Evidente, A.; Punzo, B.; Andolfi, A.; Berestetskiy, A.; Motta, A. Alternethanoxins A and B, polycyclic ethanones produced by Alternaria sonchi, potential mycoherbicides for Sonchus arvensis biocontrol. J. Agric. Food Chem. 2009, 57, 6656–6660. [Google Scholar]
- Robeson, D.J.; Strobel, G.A. αβ-Dehydrocurvularin and curvularin from Alternaria cineraiae. Z. Naturforsch., C:. J. Biosci. 1981, 36C, 1081–1083. [Google Scholar]
- Hyeon, S.-B.; Ozaki, A.; Suzuki, A.; Tamura, S. Isolation of αβ-dehydrocurvularin and β-hydroxycurvularin from Alternaria tomato as sporulation-suppressing factors. Agric. Biol. Chem. 1976, 40, 1663–1664. [Google Scholar] [CrossRef]
- Liu, Y.; Li, Z.; Vederas, J.C. Biosynthetic incorporation of advanced precursors into dehydrocurvularin, a polyketide phytotoxin from Alternaria cinerariae. Tetrahedron 1998, 54, 15937–15958. [Google Scholar] [CrossRef]
- Vurro, M.; Evidente, A.; Andolfi, A.; Zonno, M.C.; Giordano, F.; Motta, A. Brefeldin A and α,β-dehydrocurvularin, two phytotoxins from Alternaria zinniae, a biocontrol agent of Xanthium occidental. Plant Sci. 1998, 138, 67–79. [Google Scholar] [CrossRef]
- Shi, J.; Zeng, Q.; Liu, Y.; Pan, Z. Alternaria sp. MG1, a resveratrol-producing fungus: isolation, identification, and optimal cultivation conditions for resveratrol production. Appl. Microbiol. Biotechnol. 2012, 95, 369–379. [Google Scholar] [CrossRef]
- Suemitsu, R.; Ohnishi, K.; Morikawa, Y.; Ideguchi, I.; Uno, H. Porritoxinol, a phytotoxin of Alternaria porri. Phytochemistry 1994, 35, 603–605. [Google Scholar]
- Matsumoto, M.; Matsutani, S.; Shigeru, S.; Kenji, Y.; Hiroshi, H.; Hayashi, F.; Terui, Y.; Nakai, H.; Uotani, N.; Kawamura, Y. Depudecin: a novel compound inducing the flat phenotype of NIH3T3 cells doubly transformed by ras- and src- oncogene, produced by Alternaria brassicicola. J. Antibiot. 1992, 45, 879–885. [Google Scholar] [CrossRef]
- Sugiyama, N.; Kashima, C.; Yamamoto, M.; Mohri, R. Altenin, a new phytopathologically toxic metabolite from Alternaria kikuchiana. Bull. Chem. Soc. Jpn. 1965, 38, 2028. [Google Scholar] [CrossRef]
- Maekawa, N.; Nishimura, S.; Kohmoto, K.; Watanabe, Y. Isolation of the host-specific toxins produced by Alternaria alternata, Strawberry pathotype. Ann. Phytopathol. Soc. Jpn. 1979, 45, 536–537. [Google Scholar]
- Hayashi, N.; Tanabe, K.; Tsuge, T.; Nishimura, S.; Kohmoto, K.; Otani, H. Determination of host-selective toxin production during spore germination of Alternaria alternata by high-performance liquid chromatography. Phytopathology 1990, 80, 1088–1091. [Google Scholar] [CrossRef]
- Abbas, H.K.; Tanaka, T.; Duke, S.O. Pathogenicity of Alternaria alternata and Fusarium moniliforme and phytotoxicity of AAL-toxin and fumonisin B1 on tomato cultivars. J. Phytopathol. 1995, 143, 329–334. [Google Scholar] [CrossRef]
- Yamagishi, D.; Akamatsu, H.; Otani, H.; Kodama, M. Pathological evaluation of host-specific AAL-toxins and fumonisin mycotoxins produced by Alternaria and Fusarium species. J. Gen. Plant Pathol. 2006, 72, 323–327. [Google Scholar] [CrossRef]
- Liu, J.Y.; Song, Y.C.; Zhang, Z.; Wang, L.; Guo, Z.J.; Zou, W.X.; Tan, R.X. Aspergillus fumigatus CY018, an endophytic fungus in Cynodon dactylon as a versatile producer of new and bioactive metabolites. J. Biotechnol. 2004, 114, 279–287. [Google Scholar] [CrossRef]
- Zhao, J.; Mou, Y.; Shan, T.; Li, Y.; Lu, S.; Zhou, L. Preparative separation of helvolic acid from the endophytic fungus Pichia guilliermondii Ppf9 by high-speed counter-current chromatography. World J. Microbiol. Biotechnol. 2012, 28, 835–840. [Google Scholar] [CrossRef]
- Van Rozendaal, E.L.M.; Kurstjens, S.J.L.; Van Beek, T.A.; Van Den Berg, R.G. Chemotaxonomy of Taxus. Phytochemistry 1999, 52, 427–433. [Google Scholar]
- Brisdelli, F.; D’Andrea, G.; Bozzi, A. Resveratrol: a natural polyphenol with multiple chemopreventive properties (review). Curr. Drug MeTable 2009, 10, 530–546. [Google Scholar] [CrossRef]
- Zhou, L.G.; Wu, J.Y. Development and application of medicinal plant tissue cultures for production of drugs and herbal medicinals in China. Nat. Prod. Rep. 2006, 23, 789–810. [Google Scholar] [CrossRef]
- Dupont, S.; Lemetais, G.; Ferreira, T.; Cayot, P.; Gervais, P.; Beney, L. Ergosterol biosynthesis: a fungal pathway for life on land. Evolution 2012, 66, 2961–2968. [Google Scholar] [CrossRef]
- Robison, S.H.; Barr, D.B. Use of biomonitoring data to evaluate methyl eugenol exposure. Environ. Health Persp. 2006, 114, 1797–1801. [Google Scholar]
- Valenzano, D.R.; Terzibasi, E.; Genade, T.; Cattaneo, A.; Domenici, L.; Cellerino, A. Resveratrol prolongs life span and retards the onset of age-related markers in a shortlived vertebrate. Curr. Biol. 2006, 16, 296–300. [Google Scholar] [CrossRef]
- Zhao, J.; Shan, T.; Mou, Y.; Zhou, L. Plant-derived bioactive compounds produced by endophytic fungi. Mini-Rev. Med. Chem. 2011, 11, 159–168. [Google Scholar] [CrossRef]
- Graniti, A. Phytotoxins and their involvement in plant diseases. Experientia 1991, 47, 751–755. [Google Scholar]
- Pedras, M.S.C.; Biesenthal, C.J.; Zaharia, I.L. Comparison of the phytotoxic activity of the phytotoxin destruxin B and four natural analogs. Plant Sci. 2000, 156, 185–192. [Google Scholar] [CrossRef]
- Howlett, B.J. Secondary metabolite toxins and nutrition of plant pathogenic fungi. Curr. Opin. Plant Biol. 2006, 9, 371–375. [Google Scholar] [CrossRef]
- Johnson, L.J.; Johnson, R.D.; Akamatsu, H.; Salamiah, A.; Otani, H.; Kohmoto, K.; Kodama, M. Spontaneous loss of a conditionally dispensable chromosome from the Alternaria alternata apple pathotype leads to loss of toxin production and pathogenicity. Curr. Genet. 2001, 40, 65–72. [Google Scholar] [CrossRef]
- Winter, C.K.; Gilchrist, D.G.; Dickman, M.B.; Jones, C. Chemistry and biological activity of AAL toxins. Adv. Exp. Med. Biol. 1996, 392, 307–316. [Google Scholar] [CrossRef]
- Brandwagt, B.F.; Mesbah, L.A.; Takken, F.L.W.; Laurent, P.L.; Kneppers, T.J.A.; Hille, J.; Nijkamp, H.J. A longevity assurance gene homolog of tomato mediates resistance to Alternaria alternata f.sp. lycopersici toxins and fumonisin B1. Proc. Natl. Acad. Sci. USA 2000, 97, 4961–4966. [Google Scholar] [CrossRef]
- Liu, B.-L.; Tzeng, Y.-M. Development and application of destruxins: a reviw. Biotechnol. Adv. 2012, 30, 1242–1254. [Google Scholar] [CrossRef]
- Pedras, M.S.C.; Yaya, E.E.; Glawischnig, E. The phytoalexins from cultivated and wild crucifers: chemistry and biology. Nat. Prod. Rep. 2011, 28, 1381–1405. [Google Scholar] [CrossRef]
- Pedras, M.S.C.; Zaharia, I.L.; Gai, Y.; Smith, K.C.; Ward, D.E. Metabolism of the host-selective toxins destruxin B and homodestruxin B: probing a plant disease resistance trait. Org. Lett. 1999, 1, 1655–1658. [Google Scholar] [CrossRef]
- Pedras, M.S.C.; Montaut, S.; Zaharia, I.L.; Gai, Y.; Ward, D.E. Transformation of the host-selective toxin destruxin B by wild crucifers: probing a detoxification pathway. Phytochemistry 2003, 64, 957–963. [Google Scholar] [CrossRef]
- Halloin, J.M.; De Zoeten, G.A.; Gaard, G.R.; Walker, J.C. Effects of tentoxin on chlorophyll synthesis and plastid structure in cucumber and cabbage. Plant Physiol. 1970, 45, 310–314. [Google Scholar] [CrossRef]
- Avni, A.; Anderson, J.D.; Hollan, N.; Rochaix, J.D.; Gromet-Elhanan, Z.; Edelman, M. Tentoxin sensitivity of chloroplasts determined by codon 83 of β subunit of proton ATPase. Science 1992, 257, 1245–1247. [Google Scholar]
- Liu, Y.-X.; Xu, X.-M.; Dai, X.-B.; Qiang, S. Alternaria alternata crofton-weed toxin: a natural inhibitor of photosystem II in Chlamydomonas reinhardtii thylakoids. J. Agric. Food Chem. 2007, 55, 5180–5185. [Google Scholar] [CrossRef]
- Haraguchi, H.; Abo, T.; Fukuda, A.; Okamura, N.; Yagi, A. Mode of phytotoxic action of altersolanols. Phytochemistry 1996, 43, 989–992. [Google Scholar] [CrossRef]
- Robeson, D.J.; Strobel, G.A. Zinniol induces chlorophyll retention in barley leaves: The selective action of a non-specific phytotoxin. Phytochemistry 1984, 23, 1597–1599. [Google Scholar] [CrossRef]
- Qui, J.A.; Castro-Concha, L.A.; Garcia-Sosa, K.; Miranda-Ham, M.L.; Pena-Rodriguez, L.M. Is zinniol a true phytotoxin? Evaluation of its activity at the cellular level against Tagetes erecta. J. Gen. Plant Pathol. 2010, 76, 94–101. [Google Scholar] [CrossRef]
- Kenfield, D.; Bunkers, G.; Strobel, G.A.; Sugawara, F. Potential new herbicides—phytotoxins from plant pathogens. Weed Technol. 1988, 2, 519–524. [Google Scholar]
- Abbas, H.K.; Duke, S.O. Phytotoxins from plant pathogens as potential herbicides. Toxin Rev. 1995, 14, 523–543. [Google Scholar] [CrossRef]
- Mallik, M.A.B. Selective isolation and screening of soil microorganisms for metabolites with herbicidal potential. J. Crop Prot. 2001, 4, 219–236. [Google Scholar] [CrossRef]
- Abbas, H.K.; Hamed, K.; Vesonder, R.F.; Boyette, C.D.; Peterson, S.W. Phytotoxicity of AAL-toxin and other compounds produced by Alternaria alternata to jimson weed (Datura stramonium). Can. J. Bot. 1993, 71, 155–160. [Google Scholar] [CrossRef]
- Ostry, V. Alternaria mycotoxins: an overview of chemical characterization, producers, toxicity, analysis and occurrence in foodstuffs. World Mycotoxin J. 2008, 1, 175–188. [Google Scholar] [CrossRef]
- Bensassi, F.; Gallerne, C.; Sharaf El Dein, O.; Hajlaoui, M.R.; Bacha, H.; Lemaire, C. Cell death induced by the Alternaria mycotoxin alternariol. Toxicol. In Vitro 2012, 26, 915–923. [Google Scholar] [CrossRef]
- Schreck, I.; Deigendesch, U.; Burkhardt, B.; Marko, D.; Weiss, C. The Alternaria mycotoxins alternariol and alternariol methyl ether induce cytochrome P450 1A1 and apoptosis in murine hepatoma cells dependent on the aryl hydrocarbon receptor. Arch. Toxicol. 2012, 86, 625–632. [Google Scholar] [CrossRef]
- Mizushina, Y.; Maeda, N.; Kuriyama, I.; Yoshida, H. Dehydroalternusin is a specific inhibitor of mammalian DNA polymerase α. Expert Opin. Inv. Drug. 2011, 20, 1523–1534. [Google Scholar] [CrossRef]
- Huang, C.; Jin, H.; Song, B.; Zhu, X.; Zhao, H.; Cai, J.; Lu, Y.; Chen, B.; Lin, Y. The cytotoxicity and anticancer mechanisms of alterporriol L, a marine bianthraquinone, against MCF-7 human breast cancer cells. Appl. Microbiol. Biotechnol. 2012, 93, 777–785. [Google Scholar] [CrossRef]
- Bury, M.; Punzo, B.; Berestetskiy, A.; Lallemand, B.; Dubois, J.; Lefranc, F.; Mathieu, V.; Andolfi, A.; Kiss, R.; Evidente, A. Evaluation of the anticancer activities of two fungal polycyclic ethanones, alternethanoxins A and B, and two of their derivatives. Int. J. Oncol. 2011, 38, 227–232. [Google Scholar]
- Moreno, M.A.P.; Alonso, I.G.; Martin de Santos, R.; Lacarra, T.G. The role of the genus Alternaria in mycotoxin production and human deseases. Nutricion Hospitalaria 2012, 27, 1772–1781. [Google Scholar]
- Zajkowski, P.; Grabarkiewicz-Szcesna, J.; Schmidt, R. Toxicity of mycotoxins produced by four Alternaria species to Artemia salina larvae. Mycotoxin Res. 1991, 7, 11–15. [Google Scholar] [CrossRef]
- Panigrahi, S.; Dallin, S. Toxicity of the Alternaria spp metabolites, tenuazonic acid, alternariol, altertoxin-I, and alternariol monomethyl ether to brine shrimp (Artemia salina L.) larvae. J. Sci. Food Agric. 1994, 66, 493–496. [Google Scholar] [CrossRef]
- Berto, P.; Belingheri, L.; Dehorter, B. Production and purification of a novel extracellular lipase from Alternaria brassicicola. Biotechnol. Lett. 1997, 19, 533–536. [Google Scholar] [CrossRef]
- Isshiki, A.; Akimitsu, K.; Nishio, K.; Tsukamoto, M.; Yamamoto, H. Purification and characterization of an endopolygalacturonase from the rough lemon pathotype of Alternaria alternata, the cause of citrus brown spot disease. Physiol. Mol. Plant Pathol. 1997, 51, 155–167. [Google Scholar] [CrossRef]
- Kulye, M.; Liu, H.; Zhang, Y.L.; Zeng, H.M.; Yang, X.F.; Qiu, D.W. Hrip1, a novel protein elicitor from necrotrophic fungus, Alternaria tenuissima, elicits cell death, expression of defence-related genes and systemic acquired resistance in tobacco. Plant Cell Envrion. 2012, 35, 2104–2120. [Google Scholar] [CrossRef]
- Saha, D.; Fetzner, R.; Burkhardt, B.; Podlech, J.; Metzler, M.; Dang, H.; Lawrence, C.; Fischer, R. Identification of a polyketide synthase required for alternariol (AOH) and alternariol-9-methyl ether (AME) formation in Alternaria alternata. PLoS ONE 2012, 7, e40456. [Google Scholar]
- Shinya, T.; Menard, R.; Kozone, I.; Matsuoka, H.; Shibuya, N.; Kauffmann, S.; Matsuoka, K.; Saito, M. Novel beta-1,3-, 1,6-oligoglucan elicitor from Alternaria alternata 102 for defense responses in tobacco. FEBS J. 2006, 273, 2421–2423. [Google Scholar] [CrossRef]
- Yang, X.; Qiu, D.; Zeng, H.; Yuan, J.; Mao, J. Purification and characterization of a glycoprotein elicitor from Alternaria tenuissima. World J. Microbiol. Biotechnol. 2009, 25, 2035–2042. [Google Scholar] [CrossRef]
- Oikawa, H.; Yamawaki, D.; Kagawa, T.; Ichihara, A. Total synthesis of AAL-toxin TA1. Tetrahedron Lett. 1999, 40, 6621–6625. [Google Scholar]
- Bobylev, M.M.; Bobyleva, L.I.; Strobel, G.A. Synthesis and bioactivity of analogs of maculosin, a host-specific phytotoxin produced by Alternaria alternata on spotted knapweed (Centaurea maculosa). J. Agric. Food Chem. 1996, 44, 3960–3964. [Google Scholar]
- Lee, S.; Aoyagi, H.; Shimohigashi, Y.; Izumiya, N.; Ueno, T.; Fukami, H. Syntheses of cyclotretradepsipeptides, AM-toxin I and its analogs. Tetrahedron Lett. 1976, 17, 843–846. [Google Scholar]
- Koch, K.; Podlech, J.; Pfeiffer, E.; Metzler, M. Total synthesis of alternariol. J. Org. Chem. 2005, 70, 3275–3276. [Google Scholar]
- Altemoller, M.; Podlech, J.; Fenske, D. Total synthesis of altenuene and isoaltenuene. Eur. J. Org. Chem. 2006, 2006, 1678–1684. [Google Scholar] [CrossRef]
- Altenoeller, M.; Podlech, J. Total synthesis of neoaltenuene. Eur. J. Org. Chem. 2009, 2009, 2275–2282. [Google Scholar]
- Geiseler, O.; Mueller, M.; Podlech, J. Synthesis of the altertoxin III framework. Tetrahedron 2013, 69, 3683–3689. [Google Scholar] [CrossRef]
- Martin, J.A.; Vogel, E. The synthesis of zinniol. Tetrahedron 1980, 36, 791–794. [Google Scholar] [CrossRef]
- Cudaj, J.; Podlech, J. Total synthesis of altenusin and alterlactone. Synlett 2012, 23, 371–374. [Google Scholar] [CrossRef]
- Beresteskiy, A.O. A review of fungal phytotoxins: from basic studies to practical use. Appl. Biochem. Microbiol. 2008, 44, 453–465. [Google Scholar] [CrossRef]
© 2013 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
Share and Cite
MDPI and ACS Style
Lou, J.; Fu, L.; Peng, Y.; Zhou, L. Metabolites from Alternaria Fungi and Their Bioactivities. Molecules 2013, 18, 5891-5935. https://doi.org/10.3390/molecules18055891
AMA Style
Lou J, Fu L, Peng Y, Zhou L. Metabolites from Alternaria Fungi and Their Bioactivities. Molecules. 2013; 18(5):5891-5935. https://doi.org/10.3390/molecules18055891
Chicago/Turabian StyleLou, Jingfeng, Linyun Fu, Youliang Peng, and Ligang Zhou. 2013. "Metabolites from Alternaria Fungi and Their Bioactivities" Molecules 18, no. 5: 5891-5935. https://doi.org/10.3390/molecules18055891
APA StyleLou, J., Fu, L., Peng, Y., & Zhou, L. (2013). Metabolites from Alternaria Fungi and Their Bioactivities. Molecules, 18(5), 5891-5935. https://doi.org/10.3390/molecules18055891
