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

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

doi:10.3389/fmicb.2023.1274358

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

Front Microbiol. 2023 Oct 27:14:1274358. doi: 10.3389/fmicb.2023.1274358. eCollection 2023.

Authors

Kyung Taek Heo¹, Byeongsan Lee^{1

2}, Gwi Ja Hwang¹, Beomcheol Park^{1

2}, Jun-Pil Jang¹, Bang Yeon Hwang², Jae-Hyuk Jang¹, Young-Soo Hong¹

Affiliations

¹ Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju-si, Republic of Korea.
² College of Pharmacy, Chungbuk National University, Cheongju-si, Republic of Korea.

Abstract

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 Streptomyces 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_1-1 and AT_1-2). The AT_1-2 domain primarily loads ethylmalonyl-CoA and malonyl-CoA for rubiflavinone and kidamycinone and rubiflavinone, respectively; however, the AT_1-1 domain contributed to the functioning of the AT_1-2 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 Streptomyces sp. W2061. This study broadens our understanding of the incorporation of atypical primer units into polyketide products.

Keywords: Streptomyces; biosynthesis; dual acyltransferase; natural products; polyketide synthase.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was financially supported by the Basic Science Research Program (NRF 2020R1I1A206871314) of the Ministry of Education and the KRIBB Research Initiative Program (KGM5292322 and KGM1222312) funded by the Ministry of Science and ICT of the Republic of Korea.