Biosynthesis of coelulatin for the methylation of anthraquinone featuring HemN-like radical S-adenosyl-L-methionine enzyme

Lishuang Nie; Tianyi Wei; Mingming Cao; Yunbin Lyu; Shaochen Wang; Zhiyang Feng

doi:10.3389/fmicb.2022.1040900

Biosynthesis of coelulatin for the methylation of anthraquinone featuring HemN-like radical S-adenosyl-L-methionine enzyme

Front Microbiol. 2022 Nov 17:13:1040900. doi: 10.3389/fmicb.2022.1040900. eCollection 2022.

Authors

Lishuang Nie¹, Tianyi Wei², Mingming Cao¹, Yunbin Lyu¹, Shaochen Wang¹, Zhiyang Feng¹

Affiliations

¹ College of Food Science and Technology, Nanjing Agricultural University, Nanjing, China.
² State Key Laboratory of Bio-Organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.

Abstract

Bacterial aromatic polyketides are usually biosynthesized by the type II polyketide synthase (PKS-II) system. Advances in deoxyribonucleic acid (DNA) sequencing, informatics, and biotechnologies have broadened opportunities for the discovery of aromatic polyketides. Meanwhile, metagenomics is a biotechnology that has been considered as a promising approach for the discovery of novel natural products from uncultured bacteria. Here, we cloned a type II polyketide biosynthetic gene cluster (BGC) from the soil metagenome, and the heterologous expression of this gene cluster in Streptomyces coelicolor M1146 resulted in the production of three anthraquinones, two of which (coelulatins 2 and 3) had special hydroxymethyl and methyloxymethyl modifications at C2 of the polyketide scaffold. Gene deletion and in vitro biochemical characterization indicated that the HemN-like radical S-adenosyl-L-methionine (SAM) enzyme CoeI exhibits methylation and is involved in C2 modification.

Keywords: aromatic polyketides; heterologous expression; radical SAM enzyme; soil metagenome; type II polyketide synthase.