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Coordinated Action of NRPS, Baeyer-Villiger Monooxygenase, and Methyltransferase Ensures the Economical Biosynthesis of Bohemamines in Streptomyces sp. CB02009

submitted on 18.02.2020, 14:07 and posted on 20.02.2020, 06:13 by Ling Liu, Sainan Li, Runze Sun, Xiangjing Qin, Jianhua Ju, Changsheng Zhang, Yanwen Duan, Yong Huang

Bohemamines (BHMs) are bacterial alkaloids containing a pyrrolizidine core with two unprecedented methyl groups. Herein we report the activation of BHMs biosynthesis in Streptomyces sp. CB02009 using a ribosome engineering approach. Identification and characterization of the bhm gene cluster reveals a coordinated action of nonribosomal peptide synthetase BhmJ, Baeyer-villiger monooxygenase BhmK and methyltransferase BhmG for BHMs biosynthesis. BhmG is responsible for the C-methylation on C-7, while the C-9 methyl group is from a non-proteinogenic amino acid (2S,5S)-5-methylproline, required for BHMs production in three model Streptomyces hosts. Our study shed light on the intricate interaction of BhmJ/BhmK/BhmG for the economical biosynthesis of BHMs in their native producer, and also unraveled that BhmJ and BhmK are competent biocatalysts in Streptomyce albus.


NSFC grants 81473124,81530092

the Chinese Ministry of Education 111 Project B0803420


Email Address of Submitting Author


Central South University



ORCID For Submitting Author


Declaration of Conflict of Interest

We declare that we have no conflict of interest.