Epipolythiodiketopiperazine and trichothecene derivatives from the NaI-containing fermentation of marine-derived Trichoderma cf. brevicompactum

• Published in: Journal of antibiotics 2020-08, Vol.73 (8), p.559-567
• Main Authors: Yamazaki, Hiroyuki, Takahashi, Ohgi, Kirikoshi, Ryota, Yagi, Akiho, Ogasawara, Teruki, Bunya, Yuki, Rotinsulu, Henki, Uchida, Ryuji, Namikoshi, Michio
• Format: Article
• Language: English
• Subjects: 639/638/403/935; 639/638/403/936; 82/16; 82/58; Amino acids; Aquatic Organisms - chemistry; Bacteriology; Biomedical and Life Sciences; Bioorganic Chemistry; Circular Dichroism - methods; Fermentation; Fermentation - physiology; Halides; Hypocreales - chemistry; Life Sciences; Medicinal Chemistry; Metabolites; Microbiology; Organic Chemistry; Piperazines - chemistry; Sesquiterpenes - chemistry; Sodium chloride; Special Feature: Article; Trichothecenes - chemistry
• ISSN: 0021-8820; 1881-1469
• DOI: 10.1038/s41429-020-0314-5

The marine-derived fungus Trichoderma sp. TPU199 (cf. Trichoderma brevicompactum ) produces pretrichodermamide A ( 1 ) and gliovirin ( 2 ), which possess a rare type of epipolythiodiketopiperazine (ETP) structure with a disulfide bridge between the α- and β-positions of two amino acid residues. We previously reported that this strain gave the halogenated ETPs, DC1149B ( 4 ), DC1149R ( 6 ), and iododithiobrevamide ( 7 ), when fermented with sodium halides (NaCl, NaBr, and NaI). Further analyses of the metabolites obtained under NaI-containing culture conditions resulted in the isolation of two new ETP derivatives ( 11 and 12 ) and three new trichothecene sesquiterpenes ( 13 – 15 ). The structures of 11 and 12 , including their absolute configurations, were elucidated based on spectroscopic data for 11 and 12 and comparisons with those for 1 and related compounds, revealing that 11 was an epimer of 1 at the C-5 position and 12 was a trithio-derivative of 11 . The structures of 13 – 15 were established by analyzing their 1D and 2D NMR data. The absolute configurations of 13 – 15 were assigned by comparing their experimental electronic circular dichroism (ECD) spectra with the calculated ECD spectrum of 13 .