A biaryl-linked tripeptide from Planomonospora reveals a widespread class of minimal RiPP gene clusters

Mitja M. Zdouc, M.M. Alanjary, Guadelupe S. Zarazúa, Sonia I. Maffioli, M. Crüsemann, M.H. Medema, Stefano Donadio, Margherita Sosio*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Microbial natural products impress by their bioactivity, structural diversity, and ingenious biosynthesis. While screening the less exploited actinobacterial genus Planomonospora, two cyclopeptides were discovered, featuring an unusual Tyr-His biaryl bridging across a tripeptide scaffold, with the sequences N-acetyl-Tyr-Tyr-His and N-acetyl-Tyr-Phe-His. Planomonospora genomes pointed toward a ribosomal synthesis of the cyclopeptide from a pentapeptide precursor encoded by 18-bp bytA, to our knowledge the smallest coding gene ever reported. Closely linked to bytA is bytO, encoding a cytochrome P450 monooxygenase likely responsible for biaryl installment. In Streptomyces, the bytAO segment was sufficient to direct production of the crosslinked N-acetylated Tyr-Tyr-His tripeptide. Bioinformatic analysis of related cytochrome P450 monooxygenases indicated that they constitute a widespread family of enzymes, and the corresponding genes are closely linked to 5-amino acid coding sequences in approximately 200 (actino)bacterial genomes, all with potential for biaryl linkage between amino acids 1 and 3. We propose the named biarylitides this family of RiPPs.
Original languageEnglish
JournalCell Chemical Biology
DOIs
Publication statusE-pub ahead of print - 14 Dec 2020

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