Isolation and Biosynthesis of Phenazine-Polyketide Hybrids from sp. KIB-H483.

Zhiyan Wang, Feng-Xian Yang, Chongxi Liu, Li Wang, Yuxin Qi, Minghang Cao, Xiaowei Guo, Jie Li, Xueshuang Huang, Jing Yang, Sheng-Xiong Huang

Journal: Journal of natural products 2022;85(5):1324-1331

PMID: 35574837

Full Text on American Chemical Society View on PubMed

Abstract

A phenazine-polyketide hybrid compound, nexphenazine A (), was isolated from sp. KIB-H483. The bioinformatic analysis of the draft genome of the producing strain and gene inactivation experiments revealed that the biosynthesis of involves a phenazine-polyketide hybrid gene cluster. The abolished production of as well as the accumulation of shunt metabolites - in mutant strain revealed the key role of the gene, which encodes an NAD(P)H-dependent ketoreductase, in nexphenazine biosynthesis. The structures and absolute configurations of the isolated intermediates were established on the basis of spectroscopic data analysis, single-crystal X-ray diffraction, chiral chromatography, and chemical conversion experiments. NpzI exhibited stereochemical selectivity in reducing the carbonyl group of . Nexphenazine biosynthesis is proposed to involve a condensation of the carboxyl group of phenazine with one molecule of methylmalonyl-CoA by a type I PKS, followed by a ketone reduction by NpzI and an unknown methylation reaction.

Address: State Key Laboratory of Phytochemistry and Plant Resources in West China and CAS Center for Excellence in Molecular Plant Sciences, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China.; University of the Chinese Academy of Sciences, Beijing 100049, People's Republic of China.; State Key Laboratory of Phytochemistry and Plant Resources in West China and CAS Center for Excellence in Molecular Plant Sciences, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China.; State Key Laboratory of Phytochemistry and Plant Resources in West China and CAS Center for Excellence in Molecular Plant Sciences, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China.; Hunan Provincial Key Laboratory for Synthetic Biology of Traditional Chinese Medicine, Hunan University of Medicine, Huaihua 418000, People's Republic of China.; Hunan Provincial Key Laboratory for Synthetic Biology of Traditional Chinese Medicine, Hunan University of Medicine, Huaihua 418000, People's Republic of China.

DOI: 10.1021/acs.jnatprod.2c00067

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https://doi.org/10.1021/acs.jnatprod.2c00067

MeSH Terms: Multigene Family, Phenazines, Polyketides, Streptomyces