Characterization of the xiamenmycin biosynthesis gene cluster in Streptomyces xiamenensis 318.

Xiamenmycin (1) is a prenylated benzopyran derivative with anti-fibrotic activity. To investigate the genetic basis of xiamenmycin biosynthesis, we performed genome mining in the xiamenmycin-producing Streptomyces xiamenensis wild-type strain 318 to identify a candidate gene cluster. The complete ge...

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Autores principales:	Yong Yang, Ling Fu, Jinlong Zhang, Linghan Hu, Minjuan Xu, Jun Xu
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f55e6d85552f439da66234acad9194bd
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spelling	oai:doaj.org-article:f55e6d85552f439da66234acad9194bd2021-11-18T08:16:12ZCharacterization of the xiamenmycin biosynthesis gene cluster in Streptomyces xiamenensis 318.1932-620310.1371/journal.pone.0099537https://doaj.org/article/f55e6d85552f439da66234acad9194bd2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24919072/?tool=EBIhttps://doaj.org/toc/1932-6203Xiamenmycin (1) is a prenylated benzopyran derivative with anti-fibrotic activity. To investigate the genetic basis of xiamenmycin biosynthesis, we performed genome mining in the xiamenmycin-producing Streptomyces xiamenensis wild-type strain 318 to identify a candidate gene cluster. The complete gene cluster, consisting of five genes, was confirmed by a series of gene inactivations and heterologous expression. Based on bioinformatics analyses of each gene and feeding experiments, we found that the structure of an intermediate xiamenmycin B (3) accumulated in a ximA inactivation mutant, allowing us to propose a biosynthetic pathway. All five of the genes in the pathway were genetically and biochemically characterized. XimA was biochemically characterized as an ATP-dependent amide synthetase, catalyzing an amide bond formation in the presence of ATP as the final step in Xiamenmycin biosynthesis. The Km value of XimA was determined to be 474.38 µM for the substrate xiamenmycin B. These studies provide opportunities to use genetic and chemo-enzymatic methods to create new benzopyran derivatives as potential therapeutic agents.Yong YangLing FuJinlong ZhangLinghan HuMinjuan XuJun XuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 6, p e99537 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yong Yang Ling Fu Jinlong Zhang Linghan Hu Minjuan Xu Jun Xu Characterization of the xiamenmycin biosynthesis gene cluster in Streptomyces xiamenensis 318.
description	Xiamenmycin (1) is a prenylated benzopyran derivative with anti-fibrotic activity. To investigate the genetic basis of xiamenmycin biosynthesis, we performed genome mining in the xiamenmycin-producing Streptomyces xiamenensis wild-type strain 318 to identify a candidate gene cluster. The complete gene cluster, consisting of five genes, was confirmed by a series of gene inactivations and heterologous expression. Based on bioinformatics analyses of each gene and feeding experiments, we found that the structure of an intermediate xiamenmycin B (3) accumulated in a ximA inactivation mutant, allowing us to propose a biosynthetic pathway. All five of the genes in the pathway were genetically and biochemically characterized. XimA was biochemically characterized as an ATP-dependent amide synthetase, catalyzing an amide bond formation in the presence of ATP as the final step in Xiamenmycin biosynthesis. The Km value of XimA was determined to be 474.38 µM for the substrate xiamenmycin B. These studies provide opportunities to use genetic and chemo-enzymatic methods to create new benzopyran derivatives as potential therapeutic agents.
format	article
author	Yong Yang Ling Fu Jinlong Zhang Linghan Hu Minjuan Xu Jun Xu
author_facet	Yong Yang Ling Fu Jinlong Zhang Linghan Hu Minjuan Xu Jun Xu
author_sort	Yong Yang
title	Characterization of the xiamenmycin biosynthesis gene cluster in Streptomyces xiamenensis 318.
title_short	Characterization of the xiamenmycin biosynthesis gene cluster in Streptomyces xiamenensis 318.
title_full	Characterization of the xiamenmycin biosynthesis gene cluster in Streptomyces xiamenensis 318.
title_fullStr	Characterization of the xiamenmycin biosynthesis gene cluster in Streptomyces xiamenensis 318.
title_full_unstemmed	Characterization of the xiamenmycin biosynthesis gene cluster in Streptomyces xiamenensis 318.
title_sort	characterization of the xiamenmycin biosynthesis gene cluster in streptomyces xiamenensis 318.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/f55e6d85552f439da66234acad9194bd
work_keys_str_mv	AT yongyang characterizationofthexiamenmycinbiosynthesisgeneclusterinstreptomycesxiamenensis318 AT lingfu characterizationofthexiamenmycinbiosynthesisgeneclusterinstreptomycesxiamenensis318 AT jinlongzhang characterizationofthexiamenmycinbiosynthesisgeneclusterinstreptomycesxiamenensis318 AT linghanhu characterizationofthexiamenmycinbiosynthesisgeneclusterinstreptomycesxiamenensis318 AT minjuanxu characterizationofthexiamenmycinbiosynthesisgeneclusterinstreptomycesxiamenensis318 AT junxu characterizationofthexiamenmycinbiosynthesisgeneclusterinstreptomycesxiamenensis318
_version_	1718422021277220864

Characterization of the xiamenmycin biosynthesis gene cluster in Streptomyces xiamenensis 318.

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