Structural basis of the complementary activity of two ketosynthases in aryl polyene biosynthesis

Abstract Aryl polyenes (APE) are one of the most widespread secondary metabolites among gram-negative bacteria. In Acinetobacter baumannii, strains belonging to the virulent global clone 2 (GC2) mostly contain APE biosynthesis genes; its relevance in elevated pathogenicity is of great interest. APE...

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Autores principales:	Woo Cheol Lee, Sungjae Choi, Ahjin Jang, Jiwon Yeon, Eunha Hwang, Yangmee Kim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0b0ca0feb3a945c29e20ebff5b53018e
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spelling	oai:doaj.org-article:0b0ca0feb3a945c29e20ebff5b53018e2021-12-02T18:50:50ZStructural basis of the complementary activity of two ketosynthases in aryl polyene biosynthesis10.1038/s41598-021-95890-y2045-2322https://doaj.org/article/0b0ca0feb3a945c29e20ebff5b53018e2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95890-yhttps://doaj.org/toc/2045-2322Abstract Aryl polyenes (APE) are one of the most widespread secondary metabolites among gram-negative bacteria. In Acinetobacter baumannii, strains belonging to the virulent global clone 2 (GC2) mostly contain APE biosynthesis genes; its relevance in elevated pathogenicity is of great interest. APE biosynthesis gene clusters harbor two ketosynthases (KSs): the heterodimeric KS-chain length factor complex, ApeO-ApeC, and the homodimeric ketoacyl-acyl carrier protein synthase I (FabB)-like KS, ApeR. The role of the two KSs in APE biosynthesis is unclear. We determined the crystal structures of the two KSs from a pathogenic A. baumannii strain. ApeO-ApeC and ApeR have similar cavity volumes; however, ApeR has a narrow cavity near the entrance. In vitro assay based on the absorption characteristics of polyene species indicated the generation of fully elongated polyene with only ApeO-ApeC, probably because of the funnel shaped active site cavity. However, adding ApeR to the reaction increases the throughput of APE biosynthesis. Mutagenesis at Tyr135 in the active site cavity of ApeR reduces the activity significantly, which suggests that the stacking of the aryl group between Tyr135 and Phe202 is important for substrate recognition. Therefore, the two KSs function complementarily in the generation of APE to enhance its production.Woo Cheol LeeSungjae ChoiAhjin JangJiwon YeonEunha HwangYangmee KimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Woo Cheol Lee Sungjae Choi Ahjin Jang Jiwon Yeon Eunha Hwang Yangmee Kim Structural basis of the complementary activity of two ketosynthases in aryl polyene biosynthesis
description	Abstract Aryl polyenes (APE) are one of the most widespread secondary metabolites among gram-negative bacteria. In Acinetobacter baumannii, strains belonging to the virulent global clone 2 (GC2) mostly contain APE biosynthesis genes; its relevance in elevated pathogenicity is of great interest. APE biosynthesis gene clusters harbor two ketosynthases (KSs): the heterodimeric KS-chain length factor complex, ApeO-ApeC, and the homodimeric ketoacyl-acyl carrier protein synthase I (FabB)-like KS, ApeR. The role of the two KSs in APE biosynthesis is unclear. We determined the crystal structures of the two KSs from a pathogenic A. baumannii strain. ApeO-ApeC and ApeR have similar cavity volumes; however, ApeR has a narrow cavity near the entrance. In vitro assay based on the absorption characteristics of polyene species indicated the generation of fully elongated polyene with only ApeO-ApeC, probably because of the funnel shaped active site cavity. However, adding ApeR to the reaction increases the throughput of APE biosynthesis. Mutagenesis at Tyr135 in the active site cavity of ApeR reduces the activity significantly, which suggests that the stacking of the aryl group between Tyr135 and Phe202 is important for substrate recognition. Therefore, the two KSs function complementarily in the generation of APE to enhance its production.
format	article
author	Woo Cheol Lee Sungjae Choi Ahjin Jang Jiwon Yeon Eunha Hwang Yangmee Kim
author_facet	Woo Cheol Lee Sungjae Choi Ahjin Jang Jiwon Yeon Eunha Hwang Yangmee Kim
author_sort	Woo Cheol Lee
title	Structural basis of the complementary activity of two ketosynthases in aryl polyene biosynthesis
title_short	Structural basis of the complementary activity of two ketosynthases in aryl polyene biosynthesis
title_full	Structural basis of the complementary activity of two ketosynthases in aryl polyene biosynthesis
title_fullStr	Structural basis of the complementary activity of two ketosynthases in aryl polyene biosynthesis
title_full_unstemmed	Structural basis of the complementary activity of two ketosynthases in aryl polyene biosynthesis
title_sort	structural basis of the complementary activity of two ketosynthases in aryl polyene biosynthesis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0b0ca0feb3a945c29e20ebff5b53018e
work_keys_str_mv	AT woocheollee structuralbasisofthecomplementaryactivityoftwoketosynthasesinarylpolyenebiosynthesis AT sungjaechoi structuralbasisofthecomplementaryactivityoftwoketosynthasesinarylpolyenebiosynthesis AT ahjinjang structuralbasisofthecomplementaryactivityoftwoketosynthasesinarylpolyenebiosynthesis AT jiwonyeon structuralbasisofthecomplementaryactivityoftwoketosynthasesinarylpolyenebiosynthesis AT eunhahwang structuralbasisofthecomplementaryactivityoftwoketosynthasesinarylpolyenebiosynthesis AT yangmeekim structuralbasisofthecomplementaryactivityoftwoketosynthasesinarylpolyenebiosynthesis
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Structural basis of the complementary activity of two ketosynthases in aryl polyene biosynthesis

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