AUTHOR=Heo Kyung Taek , Lee Byeongsan , Hwang Gwi Ja , Park Beomcheol , Jang Jun-Pil , Hwang Bang Yeon , Jang Jae-Hyuk , Hong Young-Soo 

TITLE=A unique dual acyltransferase system shared in the polyketide chain initiation of kidamycinone and rubiflavinone biosynthesis

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1274358

DOI=10.3389/fmicb.2023.1274358

ISSN=1664-302X

ABSTRACT=<p>The pluramycin family of natural products has diverse substituents at the C2 position, which are closely related to their biological activity. Therefore, it is important to understand the biosynthesis of C2 substituents. In this study, we describe the biosynthesis of C2 moieties in <italic>Streptomyces</italic> sp. W2061, which produces kidamycin and rubiflavinone C-1, containing anthrapyran aglycones. Sequence analysis of the loading module (Kid13) of the PKS responsible for the synthesis of these anthrapyran aglycones is useful for confirming the incorporation of atypical primer units into the corresponding products. Kid13 is a ketosynthase-like decarboxylase (KSQ)-type loading module with unusual dual acyltransferase (AT) domains (AT<sub>1-1</sub> and AT<sub>1-2</sub>). The AT<sub>1-2</sub> domain primarily loads ethylmalonyl-CoA and malonyl-CoA for rubiflavinone and kidamycinone and rubiflavinone, respectively; however, the AT<sub>1-1</sub> domain contributed to the functioning of the AT<sub>1-2</sub> domain to efficiently load ethylmalonyl-CoA for rubiflavinone. We found that the dual AT system was involved in the production of kidamycinone, an aglycone of kidamycin, and rubiflavinone C-1 by other shared biosynthetic genes in <italic>Streptomyces</italic> sp. W2061. This study broadens our understanding of the incorporation of atypical primer units into polyketide products.</p>