Discovery and Biosynthesis of Cihunamides, Macrocyclic Antibacterial RiPPs with a Unique C−N Linkage Formed by CYP450 Catalysis
- 주제(키워드) Antibacterial Natural Products , Biosynthesis , Cytochrome P450 Enzymes , RIPPs , Structural Elucidation
- 등재 SCIE, SCOPUS
- 발행기관 John Wiley and Sons Inc
- 발행년도 2023
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000209699
- 본문언어 영어
- Published As https://doi.org/10.1002/anie.202300998
- PubMed 37114290
초록/요약
Cihunamides A–D (1–4), novel antibacterial RiPPs, were isolated from volcanic-island-derived Streptomyces sp. The structures of 1–4 were elucidated by 1H, 13C, and 15N NMR, MS, and chemical derivatization; they contain a tetrapeptide core composed of WNIW, cyclized by a unique C−N linkage between two Trp units. Genome mining of the producer strain revealed two biosynthetic genes encoding a cytochrome P450 enzyme and a precursor peptide. Heterologous co-expression of the core genes demonstrated the biosynthesis of cihunamides through P450-mediated oxidative Trp-Trp cross-linking. Further bioinformatic analysis uncovered 252 homologous gene clusters, including that of tryptorubins, which possess a distinct Trp-Trp linkage. Cihunamides do not display the non-canonical atropisomerism shown in tryptorubins, which are the founding members of the “atropitide” family. Therefore, we propose to use a new RiPP family name, “bitryptides”, for cihunamides, tryptorubins, and their congeners, wherein the Trp-Trp linkages define the structural class rather than non-canonical atropisomerism. © 2023 Wiley-VCH GmbH.
more