Stable Isotope-Guided Metabolomics Reveals Polar-Functionalized Fatty-Acylated RiPPs from Streptomyces

• DOI: 10.1021/acschembio.2c00601
• Publication Date: 2022-09-16T19:25:26Z
• Authors: Shumpei Asamizu; Shinta Ijichi; Shotaro Hoshino; Hansaem Jo; Hidenori Takahashi; Yuko Itoh; Sohkichi Matsumoto; Hiroyasu Onaka
• Keywords: Corynebacterium glutamicum; Moiety

Ribosomally synthesized and posttranslationally modified peptides (RiPPs) with polar-functionalized fatty acyl groups are a rarely found untapped class of natural products. Although fatty-acylated RiPPs (PFARs) have potential as antimicrobial agents, the repertoire is still limited. Therefore, expanding chemical space expected to contribute development pharmaceutical agents. In this study, we performed genome mining stable isotope-guided comparative metabolomics discover new PFAR We focused on feature that PFARs incorporate l-arginine or l-lysine starter unit group fed 13C6,15N4-l-arginine 13C6,15N2-l-lysine bacterial cultures. Metabolites were extracted compared those from nonlabeled identified putative successfully isolated solabiomycin A B Streptomyces lydicus NBRC 13 058 albopeptin nigrescens HEK616, which contained sulfoxide in labionin moiety. The gene disruption experiment indicated solS, encodes flavin adenine dinucleotide (FAD)–nicotinamide (phosphate) (NAD(P))-binding protein, involved sulfoxidation aryl sulfides. solabiomycins showed antibacterial activity against Gram-positive bacteria, including Mycobacterium tuberculosis H37Rv minimum 95% inhibitory concentration (MIC95) 3.125 μg/mL, suggesting their antituberculosis