*2.6. Aspergillus sp. Derived from Sponges and Their Antimicrobial Activities*

One hydroxypyrrolidine alkaloid preussin (**51**) was isolated and identified from marine sponge-related fungus *A. candius* KUFA 0062 (Figure 6). Preussin showed inhibition against vancomycin-resistant *Enterococcus* (VRE) and MRSA, as well as *E. faecalis* ATCC29212 and *S. aureus* ATCC 29213 [65].

Four antimicrobial compounds were isolated from the marine sponge-derived fungus *Aspergillu flavus* KUFA1152. These compounds were aspulvinones B', H, R and S (**52**–**55**). Aspulvinones B', H, R and S showed antibacterial activity against some multidrug-resistant strains isolated from the environment, and inhibited the biofilm formation of strains. Aspulvinones B' and H displayed activity with MIC values of 16 μg/mL for the *S. aureus*, and for *E. faecalis*, MIC values ranged from 16 to 64 μg/mL. Aspulvinones R and S exhibited the potent activity against all Gram-positive strains tested, with MIC values ranging from 4 to 16 μg/mL for *S. aureus* and *E. faecalis*, and from 8 to 16 μg/mL for the VRE and MRSA [66].

**Figure 6.** Compounds of *Aspergillus* sp. derived from sponges.

The endophytic fungus *A. niger* L14 has been chemically studied, and two dimers, naphtho-γ-pyrone, fonsecinone A (**56**) and isoaurasperone A (**57**), have been isolated. These compounds had obvious inhibitory effects on human pathogenic bacteria *Helicobacter pylori* 159 and G27 with MIC values ≤ 4 μg/mL, comparable to the antibacterial effect of ampicillin sodium [67].

One antimicrobial compound, namely dizinc hydroxy-neotriamycin (**58**), was isolated from the sponge-related fungus *A. ochraceopetaliformis* SCSIO 41018. Dizinchydroxyneoaspergillin showed potent inhibition against MRSA, *Acinetobacter baumannii*, *E. faecalis*, *Staphyloccocus aureus* and *Klebsiella pneumonia*, with MIC values ranging from 0.45 to 7.8 μg/mL [68].

Two new chlorinated biphenyls, including aspergetherins A and C (**59** and **60**), and two known biphenyl derivatives, including methyl 3, 5-dichloroasterric acid (**61**) and methyl chloroasterrate (**62**), were isolated from a marine sponge symbiotic fungus *A. terreus* 164018. The antibacterial activity of these compounds against MRSA was evaluated, with MIC values ranging from 1.0 to 128 μg/mL. Notably, compound **61** had obvious inhibitory effects on two different MRSA strains, with MIC values of 1 and 16 μg/mL [69].

Chemical studies of the natural compounds of the marine fungus *Aspergillus* sp. LS57 had resulted in the isolation of aspergilluone A (**63**). The MIC value of aspergilluone A was 32 μg/mL against *Mycobacterium tuberculosis*, 64 μg/mL against *S. aureus*, and 128 μg/mL against both Gram-positive *B. subtilis* and Gram-negative *E. coli* [70].

Two novel tetracyclic skeleton alkaloids were isolated from *Aspergillus* sp. LS116, which were perinadines B and C (**64** and **65**). Perinadines B and C showed moderate antibacterial activity for *B. subtilis* with MIC values of 32 and 64 μg/mL [71].

In conclusion, *Aspergillus* and its active metabolites of sponge were summarized in this paper. Sponges are the most primitive marine animals with a large number of microorganisms, which are important sources of active natural products. Fifteen antibacterial compounds were found in seven fungi strains derived from sponge. *Aspergillus* derived from sponge was the source of antimicrobial compounds. Most of the compounds had a wide antimicrobial spectrum against a variety of bacteria and fungi. Hydroxy-neotriamycin (**58**) had a strong bacteriostatic effect on a variety of bacterial pathogens.

#### *2.7. Aspergillus sp. from Seawater and Their Antimicrobial Activities*

Nine antimicrobial compounds were isolated from marine fungus *A. fumigatus* H22. These compounds included 12,13-dihydroxyfumitremorgin C (**66**), fumitremorgin B (**67**), 13 oxofumitremorgin B (**68**), fumagillin (**69**), helvolic acid (**70**), 6-O-propionyl-16-Odeacetylhelvolic acid (**71**), 16-O-propionyl-6-O-deacetylhelvolic acid (**72**), penibenzophenone E (**73**) and sulochrin (**74**) (Figure 7). Compounds **66** and **68** showed potent antibacterial activity, and **69**–**74** exhibited strong anti-MRSA activity with MIC values between 1.25 and 2.5 μM. Additionally, compound **66** showed moderate inhibitory activity against *Mycobacterium Bovis*, with an MIC value of 25 μM, and compound **67** showed moderate inhibitory activity against *C. albicans*, with an MIC value of 50 μM [72].

**Figure 7.** Compounds of *Aspergillus* sp. derived from seawater.

Three novel phenolic polyketones, namely unguidepside C (**75**), aspersidone B (**76**) and agonodepside C (**77**), were isolated from *A. unguis*. These compounds showed a strong activity against Gram-positive bacteria, with MIC ranging from 5.3 to 22.1 μM [73].

Five novel dimeric tetrahydroxanthones, including aculeaxanthones A-E, were extracted from the marine fungus *A. aculeatinus* WHUF0198. Among them, only aculeaxanthone A (**78**) showed activity against *B. subtilis* 168, *S. aureus* USA300, *H. pylori* 159, *H. pylori* 129, *H. pylori* 26695 and *H. pylori* G27, with MIC values of 1.0, 2.0, 2.0, 2.0, 4.0 and 4.0 μg/mL, respectively [74].

In conclusion, *Aspergillus* and its active metabolites from seawater were summarized. Thirteen antimicrobial compounds were found in three fungi strains derived from seawater. Compounds **69**–**74** exhibited strong anti-MRSA activity and aculeaxanthone A (**78**) showed strong anti-bacterial pathogen activity.

### *2.8. Aspergillus sp. from Marine Sediments and Their Antimicrobial Activities*

Six known compounds, including cyclopiamide (**79**), speradine H (**80**), speradine G (**81**), speradine B (**82**), speradine C (**83**) and cyclopiazonic acid (CPA) (**84**), were isolated from *A. flavus* SCSIO F025 from deep-sea sediments in the South China Sea (Figure 8). Compounds **79**–**84** showed weak antibacterial activity against *E. coli*, and CPA also exhibited strong antibacterial activity against MRSA, *B. subtilis*, *S. aureus*, *M. luteus* and *Bacillus thuringiensis* [75].

**Figure 8.** Compounds of *Aspergillus* sp. derived from marine sediments.

Five novel antibacterial metabolites and one known antibacterial compound were all isolated from the deep-sea sediment-derived fungus *A. fumigatus* SD-406. The novel metabolites included secofumitremorgins A and B (**85a** and **85b**), 29-hydroxyfumiquinazoline C (**86**), 10*R*-15-methylpseurotin A (**87**), 1,4,23-trihydroxy-hopan-22,30-diol (**88**) and sphingofungin I (**89**), and one known cyclotryprostatin B (**90**). Compounds **85**–**90** exhibited inhibitory activities against pathogenic bacteria and plant pathogenic fungi, with MIC values of 4–64 μg/mL [76].

One new metabolite, namely 3, 5-dimethylorsellinic acid-based meroterpenoid (**91**), was isolated from the deep-sea fungus *Aspergillus* sp. CSYZ-1. Compound **91** showed strong antimicrobial activity against *S. aureus* and *H. pylori*, with MIC values of 2–16 and 1–4 μg/mL, respectively [77].

Two novel antibacterial metabolites, including aspergiloxathene A (**92**) and Δ2 -1 dehydropenicillide (**93**) and one known antibacterial compound, namely dehydropenicillide (**94**), were isolated from *Aspergillus* sp. IMCASMF180035. Aspergiloxathene A exhibited significant inhibition against MRSA and *S. aureus*, with MIC values of 22.40 and 5.60 μM. Dehydropenicillide and Δ2 -1 -dehydropenicillide showed potent antibacterial activities against *H. pylori*, with MIC values of 21.61 and 21.73 μM, respectively [30].

One alkaloid asperthrin A (**95**) had been isolated from the marine endophytic fungus *Aspergillus* sp. YJ191021. The isolated compound had inhibitory effects on *Rhizoctonia solani*, *Xanthomonas oryzae* pv. *Oryzicola* and *Vibrio anguillarum*, with MIC values of 25, 12.5 and 8 μg/mL, respectively [78].

Three antimicrobial compounds were isolated from the fermented extracts of *Aspergillus* sp. WHUF05236. They included 6,8-di-O-methylversicolorin A (**96**), 6,8,1 -tri-O-methylaverantin (**97**) and 6,8-di-O-methylaverantin (**98**). They exhibited antibacterial activity against *H. pylori*, with MIC values ranging from 20.00 to 43.47 μM [79].

In conclusion, *Aspergillus* and its active metabolites from marine sediments were summarized. Twenty antimicrobial compounds were found in six *Aspergillus* strains from marine sediments. According to the literature, more than fifty antimicrobial compounds were produced by *Aspergillus* from marine sediments between 2018 and 2020. Therefore, marine sediments are an important source of secondary metabolites of fungi. Among them, compound **91** showed strong antimicrobial activity against *S. aureus* and *H. pylori*.

Sources and activities of compounds from marine *Aspergillus* were summarized in Table 1. We classified fungi and compounds according to *Aspergillus* origin.


**Table 1.** Sources and activities of compounds from marine *Aspergillus*.



In recent years, marine fungi have attracted the attention of researchers due to their bioactive compounds [10,44,46,80–85]. Combined with a series of previous excellent literature reviews, we conducted a comprehensive literature review of antibacterial compounds produced by Aspergillus fungi of different marine origin during the period of 2021–2023. The reported numbers of *Aspergillus* from marine animals, plants, mangroves, seagrasses, coral, sponge, seawater and marine sediment are shown in Figure 9. The most *Aspergillus* was derived from sponges, accounting for 23.30%. *Aspergillus* derived from marine coral was found in the second place, accounting for 16.7%.

**Figure 9.** The proportion of Aspergillus from different marine sources.

We summarized ninety-eight antibacterial compounds from *Aspergillus* strains isolated from different marine sources (Figure 10). Among them, twenty-two antimicrobial compounds were found in marine corals from January 2021 to March 2023. Marine sediments had the next highest number of antimicrobial compounds, with twenty compounds. Therefore, in recent years, the antimicrobial compounds of *Aspergillus* from marine sources mainly came from marine corals and marine sediments. Marine natural products are rich in species and play an obvious role in the treatment of pathogen infections [86–92]. More and more novel compounds with different chemical structures and biological activities are being discovered [48,93–99].

**Figure 10.** The proportion of *Aspergillus* compounds from different marine sources.
