A unique dual acyltransferase system shared in the polyketide chain initiation of kidamycinone and rubiflavinone biosynthesis
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....
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Frontiers Media S.A.
2023-10-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1274358/full |
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author | Kyung Taek Heo Byeongsan Lee Byeongsan Lee Gwi Ja Hwang Beomcheol Park Beomcheol Park Jun-Pil Jang Bang Yeon Hwang Jae-Hyuk Jang Young-Soo Hong |
author_facet | Kyung Taek Heo Byeongsan Lee Byeongsan Lee Gwi Ja Hwang Beomcheol Park Beomcheol Park Jun-Pil Jang Bang Yeon Hwang Jae-Hyuk Jang Young-Soo Hong |
author_sort | Kyung Taek Heo |
collection | DOAJ |
description | 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 (AT1-1 and AT1-2). The AT1-2 domain primarily loads ethylmalonyl-CoA and malonyl-CoA for rubiflavinone and kidamycinone and rubiflavinone, respectively; however, the AT1-1 domain contributed to the functioning of the AT1-2 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. |
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publishDate | 2023-10-01 |
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series | Frontiers in Microbiology |
spelling | doaj.art-8e6ba0db4d6944e5b23c3890d13d3c882023-10-27T22:27:34ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2023-10-011410.3389/fmicb.2023.12743581274358A unique dual acyltransferase system shared in the polyketide chain initiation of kidamycinone and rubiflavinone biosynthesisKyung Taek Heo0Byeongsan Lee1Byeongsan Lee2Gwi Ja Hwang3Beomcheol Park4Beomcheol Park5Jun-Pil Jang6Bang Yeon Hwang7Jae-Hyuk Jang8Young-Soo Hong9Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju-si, Republic of KoreaChemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju-si, Republic of KoreaCollege of Pharmacy, Chungbuk National University, Cheongju-si, Republic of KoreaChemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju-si, Republic of KoreaChemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju-si, Republic of KoreaCollege of Pharmacy, Chungbuk National University, Cheongju-si, Republic of KoreaChemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju-si, Republic of KoreaCollege of Pharmacy, Chungbuk National University, Cheongju-si, Republic of KoreaChemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju-si, Republic of KoreaChemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju-si, Republic of KoreaThe 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 (AT1-1 and AT1-2). The AT1-2 domain primarily loads ethylmalonyl-CoA and malonyl-CoA for rubiflavinone and kidamycinone and rubiflavinone, respectively; however, the AT1-1 domain contributed to the functioning of the AT1-2 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.https://www.frontiersin.org/articles/10.3389/fmicb.2023.1274358/fullbiosynthesisnatural productspolyketide synthasedual acyltransferaseStreptomyces |
spellingShingle | Kyung Taek Heo Byeongsan Lee Byeongsan Lee Gwi Ja Hwang Beomcheol Park Beomcheol Park Jun-Pil Jang Bang Yeon Hwang Jae-Hyuk Jang Young-Soo Hong A unique dual acyltransferase system shared in the polyketide chain initiation of kidamycinone and rubiflavinone biosynthesis Frontiers in Microbiology biosynthesis natural products polyketide synthase dual acyltransferase Streptomyces |
title | A unique dual acyltransferase system shared in the polyketide chain initiation of kidamycinone and rubiflavinone biosynthesis |
title_full | A unique dual acyltransferase system shared in the polyketide chain initiation of kidamycinone and rubiflavinone biosynthesis |
title_fullStr | A unique dual acyltransferase system shared in the polyketide chain initiation of kidamycinone and rubiflavinone biosynthesis |
title_full_unstemmed | A unique dual acyltransferase system shared in the polyketide chain initiation of kidamycinone and rubiflavinone biosynthesis |
title_short | A unique dual acyltransferase system shared in the polyketide chain initiation of kidamycinone and rubiflavinone biosynthesis |
title_sort | unique dual acyltransferase system shared in the polyketide chain initiation of kidamycinone and rubiflavinone biosynthesis |
topic | biosynthesis natural products polyketide synthase dual acyltransferase Streptomyces |
url | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1274358/full |
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