Adiponectin-Secretion-Promoting Cyclic Peptide–Polyketide Hybrids from a Halophyte-Associated Fungus, Colletotrichum gloeosporioides JS0417

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2022-03, Vol.85 (3), p.501-510
• Main Authors: Lee, Changyeol, Gong, Junpyo, Kim, Jaekyeong, Ko, Hyejin, An, Seungchan, Bang, Sunghee, Deyrup, Stephen T, Noh, Minsoo, Shim, Sang Hee
• Format: Article
• Language: English
• Subjects: Adiponectin; Colletotrichum; Depsipeptides; Peptides, Cyclic - pharmacology; Polyketides - pharmacology; Salt-Tolerant Plants
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.1c01102

Three new cyclic peptide–polyketide hybrids (1–3) and two new chaetiacandin-type polyketides (4 and 5) along with nine known compounds were isolated from cultures of a halophyte-associated fungus, Colletotrichum gloeosporioides JS0417. Spectroscopic analysis revealed that 1–3 were cyclic depsipeptides where 3,5,11-trihydroxy-2,6-dimethyl­dodecanoic acid was linked to two amino acids through amide and ester bonds to form a 12-membered ring. Relative and absolute configurations for the peptides were determined with spectroscopic analysis and chemical reactions. The cyclic depsipeptides 2 and 6 were determined to act as strong adiponectin-secretion-promoting modulators with potential to treat metabolic diseases associated with hypoadiponectinemia. Notably, a known compound, tryptophol, significantly inhibited PGE2 synthesis and also promoted adiponectin secretion, exhibiting a similar biological activity profile to aspirin, but with greater potency. The presence of an isoleucine moiety and non-glycosylation may be important for biological activity of the cyclic peptide–polyketide hybrids, and non-methoxylation of the side chain may influence activity of the indole derivatives.