New Antibacterial Peptaibiotics against Plant and Fish Pathogens from the Deep-Sea-Derived Fungus Simplicillium obclavatum EIODSF 020.

Bacterial diseases could severely harm agricultural production. To develop new antibacterial agents, the secondary metabolites of a deep-sea-derived fungus Simplicillium obclavatum EIODSF 020 with antibacterial activities against plant and fish pathogens were investigated by a bioassay-guided approach, which led to the isolation of 11 new peptaibiotics, simplicpeptaibs A-K ( 1 - 11 ). They contain 16-19 residues, including β-alanine, tyrosine, or tyrosine O -sulfate, that were rarely present in peptaibiotics. Their structures were elucidated by spectroscopic analyses (NMR, HRMS, HRMS2 , and ECD) and Marfey's method. The primary and secondary structures of novel sulfated peptaibiotic 9 were reconfirmed by single-crystal X-ray diffraction analysis. Genome sequencing of S. obclavatum EIODSF 020 allowed the detection of a gene cluster encoding two individual NRPSs (totally containing 19 modules) that was closely related to simplicpeptaib biosynthesis. Antibacterial investigations of 1 - 11 together with the previously isolated linear and cyclic peptides from this strain suggested the antibacterial property of this fungus was attributed to the peptaibiotics and cyclic lipopeptides. Among them, compounds 4 , 6 , 7 , and 9 showed significant activity against the tobacco pathogen Ralstonia solanacearum or tilapia pathogens Streptococcus iniae and Streptococcus agalactiae . The antibacterial activity of 6 against R. solanacearum could be enhanced by the addition of 1% NaCl. The structure-bioactivity relationship of simplicpeptaibs was discussed.