**1. Introduction**

Sulfur is one of the prime elements on Earth and the eighth most abundant element in the human body. It is a group 6A (or VIA) member of the periodic table, with a larger atomic size and a weaker electronegativity than oxygen. Sulfur has unique characteristics, such as five different oxidation states, and sulfur-containing molecules often participate in biological redox reactions and electron transfer processes. Notably, two essential amino acids, L-methionine and L-cysteine, both contain a sulfur atom, further highlighting the importance and indispensability of sulfur in biology [1]. Indeed, one fifth (20%) of the FDA-approved drugs contain at least one sulfur atom. These sulfur-containing drugs have different structure skeletons such as sulfonamides, β-lactams, thioethers, thiazoles, thiophenes, phenothiazines, sulfoxides, S=C and S=P structures, thionucleotides, sulfones, sulfates and macrocyclic disulfides. Of note, many sulfur-containing drugs are natural products or their derivatives (i.e., rosuvastatin, ecteinascidin 743 and ixabepilone) [2].

Fungi are a major group of microorganisms that produce a broad array of compounds with novel structures and unique bioactivities. One type of fungi colonizes the intercellular and/or intracellular regions of healthy plant tissues at a particular time and has no interference with and causes no pathogenic symptoms to the host [3]. These endophytic microorganisms are an important but less-explored source for the discovery of structurally novel natural products in drug research. This paper reviews new sulfur-containing compounds isolated from endophytic fungi since 1985 (Table 1). Based on their major chemical

**Citation:** Fan, Y.; Ma, Z.; Zhang, Y.; Wang, Y.; Ding, Y.; Wang, C.; Cao, S. Sulfur-Containing Compounds from Endophytic Fungi: Sources, Structures and Bioactivities. *J. Fungi* **2022**, *8*, 628. https://doi.org/ 10.3390/jof8060628

Academic Editors: Tao Feng and Frank Surup

Received: 29 May 2022 Accepted: 10 June 2022 Published: 13 June 2022

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2022 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 (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

features, these compounds will be categorized into peptides, disulfides, polyketides, hybrids and terpenoids. The fungal strains that producing sulfur-containing compounds, host plants, structure uniqueness and biological activities of these compounds will be discussed (Table 1). taining compounds isolated from endophytic fungi since 1985 (Table 1). Based on their major chemical features, these compounds will be categorized into peptides, disulfides, polyketides, hybrids and terpenoids. The fungal strains that producing sulfur-containing compounds, host plants, structure uniqueness and biological activities of these compounds will be discussed (Table 1). taining compounds isolated from endophytic fungi since 1985 (Table 1). Based on their major chemical features, these compounds will be categorized into peptides, disulfides, polyketides, hybrids and terpenoids. The fungal strains that producing sulfur-containing compounds, host plants, structure uniqueness and biological activities of these comtaining compounds isolated from endophytic fungi since 1985 (Table 1). Based on their major chemical features, these compounds will be categorized into peptides, disulfides, polyketides, hybrids and terpenoids. The fungal strains that producing sulfur-containing compounds, host plants, structure uniqueness and biological activities of these comtaining compounds isolated from endophytic fungi since 1985 (Table 1). Based on their major chemical features, these compounds will be categorized into peptides, disulfides, polyketides, hybrids and terpenoids. The fungal strains that producing sulfur-containing compounds, host plants, structure uniqueness and biological activities of these compounds will be discussed (Table 1). taining compounds isolated from endophytic fungi since 1985 (Table 1). Based on their major chemical features, these compounds will be categorized into peptides, disulfides, polyketides, hybrids and terpenoids. The fungal strains that producing sulfur-containing compounds, host plants, structure uniqueness and biological activities of these comtaining endophytic fungi 1). their major features, will categorized peptides, disulfides, polyketides, terpenoids. The compounds, plants, and pounds will discussed (Table

structurally novel natural products in drug research. This paper reviews new sulfur-con-

structurally novel natural products in drug research. This paper reviews new sulfur-con-

structurally novel in drug This paper new sulfur-con-

structurally novel natural products in drug research. This paper reviews new sulfur-con-

structurally novel natural products in drug research. This paper reviews new sulfur-con-

structurally novel natural products in drug research. This paper reviews new sulfur-con-

**Table 1.** Sulfur-containing compounds isolated from plant endophyte fungi. pounds will be discussed (Table 1).

pounds will be discussed (Table 1).

pounds will be discussed (Table 1).

*J. Fungi* **2022**, *8*, x FOR PEER REVIEW 2 of 36

*J. Fungi* **2022**, *8*, x FOR PEER REVIEW 2 of 36

*J. Fungi* **2022**, *8*, x FOR PEER REVIEW 2 of 36

*J. Fungi* **2022**, *8*, x FOR PEER REVIEW 2 of 36

*J. Fungi* **2022**, *8*, x FOR PEER REVIEW 2 of 36

*J. Fungi* **2022**, *8*, x FOR PEER REVIEW 2 of 36


**Table 1.** *Cont*. *J. Fungi* **2022**, *8*, x FOR PEER REVIEW 3 of 36 *J. Fungi* **2022**, *8*, x REVIEW 3 of 36 *J. Fungi* **2022**, *8*, x FOR PEER REVIEW 3 of 36 *J. Fungi* x FOR PEER REVIEW 3 36


#### **Table 1.** *Cont*. *J. Fungi* **2022**, *8*, x FOR PEER REVIEW 4 of 36 *J. Fungi* **2022**, *8*, x FOR PEER REVIEW 4 of 36 *J. Fungi* **2022**, *8*, x FOR PEER REVIEW 4 of 36

*J. Fungi* **2022**, *8*, x FOR PEER REVIEW 5 of 36

*J. Fungi* **2022**, *8*, x FOR PEER REVIEW 5 of 36

#### **Table 1.** *Cont*. *J. Fungi* **2022**, *8*, x FOR PEER REVIEW 5 of 36 *J. Fungi* **2022**, *8*, x FOR PEER REVIEW 5 of 36 *J. Fungi* **2022**, *8*, x FOR PEER REVIEW 5 of 36 *J. Fungi* **2022**, *8*, x FOR PEER REVIEW 5 of 36 *J. Fungi* **2022**, *8*, x FOR PEER REVIEW 5 of 36

*J. Fungi* **2022**, *8*, 628


**Table 1.** *Cont*. *J. Fungi* **2022**, *8*, x FOR PEER REVIEW 6 of 36 *J. Fungi* **2022**, *8*, x FOR PEER REVIEW 6 of 36 *J. Fungi* **2022**, *8*, x FOR PEER REVIEW 6 of 36 *J. Fungi* **2022**, *8*, x FOR PEER REVIEW 6 of 36 *J. Fungi* **2022**, *8*, 628

**Table 1.** *Cont*. *J. Fungi* **2022**, *8*, x FOR PEER REVIEW 7 of 36 *J. Fungi* **2022**, *8*, x FOR PEER REVIEW 7 of 36 *J. Fungi* **2022**, *8*, x FOR PEER REVIEW 7 of 36

*aegyptium* [23]

*aegyptium* [23]

*aegyptium* [23]

*aegyptium* [23]

*aegyptium* [23]

*Exserohilum holmii Dactyloctenium* 

*Exserohilum holmii Dactyloctenium* 

*Exserohilum holmii Dactyloctenium* 

*Exserohilum holmii Dactyloctenium* 

*Exserohilum holmii Dactyloctenium* 

*Exserohilum holmii Dactyloctenium* 

OH H

H O

N N

**51**

O S

S O

H OH

H

O


*J. Fungi* **2022**, *8*, x FOR PEER REVIEW 7 of 36

Root of *Sonneratia* 

Fresh tissue of the marine mangrove plant *Avicennia marina*

*caseolaris* [21]

Antimicrobial [22]

*Penicillium janthinellum* HDN13-309

*Penicillium brocae* MA-231

#### **Table 1.** *Cont*.

*Bionectria* sp. Y1085 *Huperzia serrata* Antibacterial [9]

*Bionectria* sp. Y1085 *Huperzia serrata* Antibacterial [9]

*Bionectria* sp. Y1085 *Huperzia* Antibacterial [9]

*Bionectria* sp. Y1085 *Huperzia serrata* Antibacterial [9]

*Bionectria* sp. Y1085 *Huperzia serrata* Antibacterial [9]

*Bionectria*sp. Y1085 *Huperzia* Antibacterial [9]


*J. Fungi* **2022**, *8*, x FOR PEER REVIEW 8 of 36

*Nigrospora sphaerica* Germinating fescue

Fresh asymptomatic leaf tissues of the medicinal plant *Costus speciosus*

> Stems of *Paris polyphylla var. yunnanensis*

seed [24]

Inhibiting porcine pancreatic alpha-amylase (**57**)

Cytotoxic [26]

[25]

#### **Table 1.** *Cont*. 0312

*Aspergillus versicolor*

*Setosphaeria rostrata* 

*rhodostegia*

*rhodostegia*

*rhodostegia*

*rhodostegia*

Inhibiting the release of β-

Inhibiting the release of β-

Inhibiting the release of β-

Inhibiting the release of β-

glucuronidase (**67**) [8]

glucuronidase (**67**) [8]

glucuronidase (**67**) [8]

glucuronidase (**67**) [8]

*Epicoccum nigrum* Leaves of *Lysidice* 

*Epicoccum nigrum* Leaves of *Lysidice* 

*Epicoccum nigrum* Leaves of *Lysidice* 

*Epicoccum nigrum* Leaves of *Lysidice* 

*J. Fungi* **2022**, *8*, x FOR PEER REVIEW 9 of 36

*J. Fungi* **2022**, *8*, x FOR PEER REVIEW 9 of 36

Apparently normal flower of *Illigera rhodantha* (Hernandiaceae)

Apparently normal flower of *Illigera rhodantha* (Hernandiaceae)

Fresh leaves of *Bixa* 

Fresh leaves of *Bixa* 

*Rhododendron tomentosum* 

*Rhododendron tomentosum* 

*orellana* L. (Bixaceae) Cytotoxic [6]

*orellana* L. (Bixaceae) Cytotoxic [6]

Cytotoxic (**64**)

Cytotoxic (**64**)

Antifungal (**64**) [7]

Antifungal (**64**) [7]

[5]

[5]

#### **Table 1.** *Cont*.

*Lasiodiplodia pseudotheobromae* 

*Lasiodiplodia pseudotheobromae* 

*Botryosphaeria mamani* 

*Botryosphaeria mamani* 

*Penicillium raciborskii* (TRT59)

*Penicillium raciborskii* (TRT59)

*Aspergillus tamarii Ficus carica* Cytotoxic

*Aspergillus tamarii Ficus carica* Cytotoxic

*Aspergillus tamarii Ficus carica* Cytotoxic

*Aspergillus tamarii Ficus carica* Cytotoxic

Fresh tissue of the marine mangrove plant *Avicennia marina*

Fresh tissue of the marine mangrove plant *Avicennia marina*

Fresh tissue of the marine mangrove plant *Avicennia marina*

Fresh tissue of the marine mangrove plant *Avicennia marina*

*harzianum Zingiber officinale* [29]

*harzianum Zingiber officinale* [29]

*harzianum Zingiber officinale* [29]

*harzianum Zingiber officinale* [29]

Antimicrobial [30]

Antimicrobial [30]

Antimicrobial [30]

Antimicrobial [30]

Cytotoxic (**75**, **76, 79** and **80**) [31]

Cytotoxic (**75**, **76, 79** and **80**) [31]

Cytotoxic (**75**, **76, 79** and **80**) [31]

Cytotoxic (**75**, **76, 79** and **80**) [31]

*Trichoderma* 

*Trichoderma* 

*Trichoderma* 

*Trichoderma* 

<sup>O</sup> <sup>N</sup>

OH

<sup>O</sup> <sup>N</sup>

<sup>O</sup> <sup>N</sup>

<sup>O</sup> <sup>N</sup>

HO

HO

HO

HO

O

O

O

O

**73**

**73**

**73**

**73**

OH<sup>H</sup> <sup>H</sup> OH

OH<sup>H</sup> <sup>H</sup> OH

OH<sup>H</sup> <sup>H</sup> OH

OH<sup>H</sup> <sup>H</sup> OH

NH

NH

NH

NH

S S

S S

S S

S S

OCH3

OCH3

OCH3

OCH3

OCH3

OCH3

OCH3

OCH3

*Penicillium brocae* MA-231

*Penicillium brocae* MA-231

*Penicillium brocae* MA-231

*Penicillium brocae* MA-231

OH

OH H

OH H

OH H O N

O N

O N N

N

S S H

N

S S H

H

H

H

H

H

H

H

OH

OH

OH

O

O

O

O

O

O

*J. Fungi* **2022**, *8*, x FOR PEER REVIEW 10 of 36

*J. Fungi* **2022**, *8*, x FOR PEER REVIEW 10 of 36

*J. Fungi* **2022**, *8*, x FOR PEER REVIEW 10 of 36

Healthy leaf tissue of

Healthy leaf tissue of

Healthy leaf tissue of

Decaying wood sample collected in Christchurch

Decaying wood sample collected in Christchurch

Decaying wood sample collected in Christchurch

*Astragalus lentiginosus* Cytotoxic [27]

*Astragalus lentiginosus* Cytotoxic [27]

*Astragalus lentiginosus* Cytotoxic [27]

Cytotoxicity [9]

Cytotoxicity [9]

Cytotoxicity [9]

#### **Table 1.** *Cont*. <sup>5926</sup>Bamboo leaf Antibacterial [28] <sup>5926</sup>Bamboo leaf Antibacterial [28] <sup>5926</sup>Bamboo leaf Antibacterial [28]

*Trichoderma* sp. BCC

*Trichoderma* sp. BCC

*Trichoderma* sp. BCC

*Emericella* sp. AST0036

*Emericella* sp. AST0036

*Emericella* sp. AST0036

*Tilachlidium* sp. (CANU-T988)

*Tilachlidium* sp. (CANU-T988)

*Tilachlidium* sp. (CANU-T988)

Root of *Sonneratia* 

Root of *Sonneratia* 

Root of *Sonneratia* 

Fresh tissue of the marine mangrove plant *Avicennia marina*

Fresh tissue of the marine mangrove plant *Avicennia marina*

Fresh tissue of the marine mangrove plant *Avicennia marina*

Cytotoxic

Cytotoxic

Cytotoxic

*caseolaris* Cytotoxic [21]

1A Submerged wood Nematicidal [32]

1A Submerged wood Nematicidal [32]

1A Submerged wood Nematicidal [32]

marine mangrove

Antimicrobial [20]

Antimicrobial [20]

[20]

Antimicrobial [20]

*Penicillium janthinellum*  HDN13-309

*janthinellum* 

*Penicillium janthinellum*  HDN13-309

*Penicillium janthinellum*  HDN13-309

*Penicillium brocae*  MA-231

*brocae* 

*Penicillium brocae*  MA-231

*Penicillium brocae*  MA-231

*Gliocladium roseum*

*Gliocladium* 

*Gliocladium roseum*

*Gliocladium roseum*

*J. Fungi* **2022**, *8*, 628

N N

N N

N N

S S

S S

S S

O

O

O

H OH

H OH

H OH

H

H

H

**79** R=( )OH, ( ) H **80** R= O

**79** R=( )OH, ( ) H **80** R= O

**79** R=( )OH, ( ) H **80** R= O

OH

OH

OH

H

H

H

R

R

R

H

H

H

OH

OH

OH

O

O

O


Mangrove plant

Mangrove plant

Mangrove plant

*Kandelia candel* [19]

*J. Fungi* **2022**, *8*, x FOR PEER REVIEW 11 of 36

*J. Fungi* **2022**, *8*, x FOR PEER REVIEW 11 of 36

*J. Fungi* **2022**, *8*, x FOR PEER REVIEW 11 of 36

**Table 1.** *Cont*. OUCMDZ-1847 OUCMDZ-1847 *Phoma* sp.

*Phoma* sp.

*Phoma* sp.

Antibacterial (**94**) Inhibiting NF-kB (**94**), iNOS (**94** and **95**)

Antibacterial (**94**) Inhibiting NF-kB (**94**), iNOS (**94** and **95**)

*neglecta* FT462 *Lycopodiella cernua* 

*neglecta* FT462 *Lycopodiella cernua* 

*J. Fungi* **2022**, *8*, x FOR PEER REVIEW 12 of 36

*J. Fungi* **2022**, *8*, x FOR PEER REVIEW 12 of 36

*J. Fungi* **2022**, *8*, x FOR PEER REVIEW 12 of 36

M336 *Huperzia serrata Trev* Cytotoxic

M336 *Huperzia serrata Trev* Cytotoxic

M336 *Huperzia serrata Trev* Cytotoxic

Antibacterial [33]

Antibacterial [33]

Antibacterial [33]
