Antifungal and Antiviral Cyclic Peptides from the Deep-Sea-Derived Fungus Simplicillium obclavatum EIODSF 020

Abstract

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.

Natural Cyclic Peptides as an Attractive Modality for Therapeutics: A Mini Review

“…The cyclic peptides simplicilliumtides J–M were identified along with a linear peptide and other known analogues verlamelins A and B from the deep-sea-derived fungal strain Simplicillium obclavatum EIODSF 020. Simplicilliumtide K exhibited significant antiviral activity toward HSV-1 with IC 50 value of 14.0 μM, and it also showed antifungal activity against Aspergillus versicolor and Curvularia australiensis [ 93 ]. Recently isolated antiviral cyclic peptides were drawn in Figure 5 .…”

Structural Diversity and Biological Activities of Cyclic Depsipeptides from Fungi

“…Simplicilliumtides J ( 280 ), K ( 281 ), L ( 282 ) and verlamelins A ( 283 ) and B ( 284 ) were isolated from the deep-sea-derived fungus Simplicillium obclavatum EIODSF 020. Simplicilliumtides J ( 280 ), and verlamelins A ( 283 ) and B ( 284 ) showed antifungal activity toward Aspergillus versicolor and Curvularia australiensis , and also had obvious antiviral activity on HSV-1 with IC 50 values of 14.0, 16.7, and 15.6 μM, respectively [ 182 ]. Verlamelins A ( 283 ) and B ( 284 ) were obtained from the entomopathogenic fungus Lecanicillium sp.…”

Anti-inflammatory potency of Locusta migratoria manilensis cyclopeptides in mast cells and macrophages

“…10 A new linear peptide, simplicilliumtide, and four new cyclic peptide simplicilliumtides from a deep-sea-derived fungus have shown signicant anti-fungal activity toward Aspergillus versicolor and Curvularia australiensis and also obvious antiviral activity toward HSV-1. 11 Both compounds from Bacillus amyloliquefaciens L-H15 have shown good inhibitory activities against three plant fungal pathogens in a cylinder-plate diffusion assay. 12 So far, more than 10 000 species of locusts have been iden-tied and are widely distributed in tropical and subtropical regions.…”