A new linear peptide simplicilliumtide I (1) and four new cyclic peptides simplicilliumtides J−M (2−5) together with known analogues verlamelins A and B (6 and 7) were isolated from the deep-sea-derived fungal strain Simplicillium obclavatum EIODSF 020. Their structures were elucidated by spectroscopic analysis, and their absolute configurations were further confirmed by chemical structural modification, Marfey's and Mosher's methods. Compounds 2, 6, and 7 showed significant antifungal activity toward Aspergillus versicolor and Curvularia australiensis and also had obvious antiviral activity toward HSV-1 with IC 50 values of 14.0, 16.7, and 15.6 μM, respectively. The structure−bioactivity relationship of this type of cyclic peptide was also discussed. This is the first time to discuss the effects of the lactone linkage and the substituent group of the fatty acid chain fragment on the bioactivity of this type of cyclic peptides. This is also the first time to report the antiviral activity of these cyclic peptides. KEYWORDS: deep-sea-derived fungus, Simplicillium obclavatum, peptide, antifungal, antiviral, structure−bioactivity relationshipFungi are important sources of novel bioactive compounds that are considered to be interesting synthetic models or important new lead compounds for medicine as well as for plant protection.1−5 Fungus Simplicillium lamellicola, previously known as Acremonium strictum BCP, was lately given the name based on 28S rRNA gene and ITS regions. A. strictum BCP could produce cyclic hexapeptide verlamelin 6 and was used as a microbial fungicide with the mechanism of mycoparasitism and antibiosis. 7−9 In our previous study, we had found eight linear peptides (namely, simplicilliumtides A− H) from a deep-sea-derived fungal strain Simplicillium obclavatum EIODSF 020. 10 Now, in our continued study, a new linear peptide simplicilliumtide I (1) and four new cyclic hexapeptides simplicilliumtides J−M (2−5) together with known analogues verlamelins A and B (6 and 7)11,12 were further isolated from the same crude extract of the fungal strain (Figure 1). Verlamelin A is a cyclic hexadepsipeptide antibiotic originally isolated from Verticillium lamellicola in 1980 11 with antifungal activity toward phytopathogenic fungi in vitro and in vivo;13,14 then it was also isolated from an entomopathogenic fungus Lecanicillium sp. HF627 in 2014 together with its analogue verlamelin B, and its absolute configuration was determined for the first time.12 At the same time a gene cluster responsible for the biosynthesis of verlamelin was also identified. 15 In this article, we report the isolation, structure elucidation, and antifungal and antiviral activities of the peptides (1−7). Their structure−bioactivity relationship is also discussed. ■ MATERIALS AND METHODSGeneral Experimental Procedures. The procedures were the same as previously reported.10 Details are described in the Supporting Information.

The fungal diversity in deep-sea environments has recently gained an increasing amount attention. Our knowledge and understanding of the true fungal diversity and the role it plays in deep-sea environments, however, is still limited. We investigated the fungal community structure in five sediments from a depth of ∼4000 m in the East India Ocean using a combination of targeted environmental sequencing and traditional cultivation. This approach resulted in the recovery of a total of 45 fungal operational taxonomic units (OTUs) and 20 culturable fungal phylotypes. This finding indicates that there is a great amount of fungal diversity in the deep-sea sediments collected in the East Indian Ocean. Three fungal OTUs and one culturable phylotype demonstrated high divergence (89%–97%) from the existing sequences in the GenBank. Moreover, 44.4% fungal OTUs and 30% culturable fungal phylotypes are new reports for deep-sea sediments. These results suggest that the deep-sea sediments from the East India Ocean can serve as habitats for new fungal communities compared with other deep-sea environments. In addition, different fungal community could be detected when using targeted environmental sequencing compared with traditional cultivation in this study, which suggests that a combination of targeted environmental sequencing and traditional cultivation will generate a more diverse fungal community in deep-sea environments than using either targeted environmental sequencing or traditional cultivation alone. This study is the first to report new insights into the fungal communities in deep-sea sediments from the East Indian Ocean, which increases our knowledge and understanding of the fungal diversity in deep-sea environments.

Two new dihydrothiophene-condensed chromones and a new natural chromone, namely oxalicumones A-C (1-3), respectively, were isolated from a culture broth of a marine-derived fungus, Penicillium oxalicum. The structures of 1-3 and acetylated derivatives of 1 (4-7) were elucidated on the basis of spectroscopic methods and chemical reactions. The absolute configuration of 1 and 2 were established by using the modified Mosher ester method and circular dichroism data of an in situ formed [Rh2(OCOCF3)4] and [Mo2(OAc)4] complex. (R)-MTPA ester of 1 showed cytotoxicity against A375, SW-620, and HeLa carcinoma cell lines with IC50 values of 8.9, 7.8, and 18.4 µM, respectively. Compound 1 displayed cytotoxicity against A375 and SW-620 cell lines with IC50 values of 11.7 and 22.6 µM, respectively. The structure-biological activity relationship of 1 was discussed.

Seventeen lactones including eight territrem derivatives (1–8) and nine butyrolactone derivatives (9–17) were isolated from a marine-derived fungus Aspergillus terreus SCSGAF0162 under solid-state fermentation of rice. Compounds 1–3 and 9–10 were new, and their structures were elucidated by spectroscopic analysis. The acetylcholinesterase inhibitory activity and antiviral activity of compounds 1–17 were evaluated. Among them, compounds 1 and 2 showed strong inhibitory activity against acetylcholinesterase with IC50 values of 4.2 ± 0.6, 4.5 ± 0.6 nM, respectively. This is the first time it has been reported that 3, 6, 10, 12 had evident antiviral activity towards HSV-1 with IC50 values of 16.4 ± 0.6, 6.34 ± 0.4, 21.8 ± 0.8 and 28.9 ± 0.8 μg·mL−1, respectively. Antifouling bioassay tests showed that compounds 1, 11, 12, 15 had potent antifouling activity with EC50 values of 12.9 ± 0.5, 22.1 ± 0.8, 7.4 ± 0.6, 16.1 ± 0.6 μg·mL−1 toward barnacle Balanus amphitrite larvae, respectively.