biostudies-literatureUnknown13Nie LBacterial 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 <i>Streptomyces coelicolor</i> M1146 resulted in the production of three anthraquinones, two of which (coelulatins <b>2</b> and <b>3</b>) had special hydroxymethyl and methyloxymethyl modifications at C2 of the polyketide scaffold. Gene deletion and <i>in vitro</i> biochemical characterization indicated that the HemN-like radical S-adenosyl-L-methionine (SAM) enzyme CoeI exhibits methylation and is involved in C2 modification.Frontiers in microbiology1040900https://www.ebi.ac.uk/biostudies/studies/S-EPMC9714029biostudies-literatureBiosynthesis of coelulatin for the methylation of anthraquinone featuring HemN-like radical S-adenosyl-L-methionine enzyme.PMC9714029Cao MFeng ZWei TLyu YWang SNie LfalseBiosynthesis of coelulatin for the methylation of anthraquinone featuring HemN-like radical S-adenosyl-L-methionine enzyme.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 <i>Streptomyces coelicolor</i> M1146 resulted in the production of three anthraquinones, two of which (coelulatins <b>2</b> and <b>3</b>) had special hydroxymethyl and methyloxymethyl modifications at C2 of the polyketide scaffold. Gene deletion and <i>in vitro</i> biochemical characterization indicated that the HemN-like radical S-adenosyl-L-methionine (SAM) enzyme CoeI exhibits methylation and is involved in C2 modification.2022-01-01T00:00:00Z20222026-05-28T21:28:58.084Z2025-04-19T22:49:28.322ZS-EPMC97140293646668110.3389/fmicb.2022.1040900