Dataset Information

Molecular Genetic Characterization of an Anthrabenzoxocinones Gene Cluster in Streptomyces Sp. FJS31-2 for the Biosynthesis of BE-24566B and Zunyimycin Ale.

ABSTRACT: Genome mining is an effective tool used to discover novel natural products from actinomycetes. Genome sequence analysis of Streptomyces sp. FJS31-2 revealed the presence of one putative type II polyketide gene cluster (ABX), which may correspond to type II polyketide products including BE-24566B and its chloro-derivatives. The addition of natural humus acid successfully activated the biosynthsis of the abx gene cluster. BE-24566B and its chloro-derivatives, named zunyimycin A, were also detected. The targeted deletion of the polyketide skeleton synthesis genes such as abxp, abxk, and abxs was performed in the wild strain to identify the gene cluster for BE-24566B biosynthesis.

SUBMITTER: Lu Y

PROVIDER: S-EPMC6273070 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Publications

Molecular Genetic Characterization of an Anthrabenzoxocinones Gene Cluster in Streptomyces Sp. FJS31-2 for the Biosynthesis of BE-24566B and Zunyimycin Ale.

Lü Yuhong Y Yue Changwu C Shao Meiyun M Qian Shengyan S Liu Ning N Bao Yuxin Y Wang Miao M Liu Minghao M Li Xiaoqian X Wang Yinyin Y Huang Ying Y

Molecules (Basel, Switzerland) 20160530 6

Genome mining is an effective tool used to discover novel natural products from actinomycetes. Genome sequence analysis of Streptomyces sp. FJS31-2 revealed the presence of one putative type II polyketide gene cluster (ABX), which may correspond to type II polyketide products including BE-24566B and its chloro-derivatives. The addition of natural humus acid successfully activated the biosynthsis of the abx gene cluster. BE-24566B and its chloro-derivatives, named zunyimycin A, were also detected ...[more]

PMID: 27248985

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Project description:Inthomycins belong to a growing family of oxazole-containing polyketides and exhibit a broad spectrum of anti-oomycete and herbicidal activities. In this study, we purified inthomycins A and B from the metabolites of Streptomyces sp. strain SYP-A7193 and determined their chemical structures. Genome sequencing, comparative genomic analysis, and gene disruption of Streptomyces sp. SYP-A7193 showed that the inthomycin biosynthetic gene cluster (itm) belonged to the hybrid polyketide synthase (PKS)/nonribosomal peptide synthetase (NRPS) system. Functional domain comparison and disruption/complementation experiments of itm12 resulted in the complete loss of inthomycins A and B and the subsequent restoration of their production, confirming that itm12 encodes a discrete acyltransferase (AT), and hence, itm was considered to belong to the trans-AT type I PKS system. Moreover, the disruption/complementation experiments of itm15 also resulted in the loss and restoration of inthomycin A and B formation. Further gene cloning, expression, purification, and activity verification of itm15 revealed that Itm15 is a cyclodehydratase that catalyzes a straight-chain dehydration reaction to form an oxazole ring for the biosynthesis of inthomycins A and B. Thus, we discovered a novel enzyme that catalyzes oxazole ring formation and elucidated the complete biosynthetic pathway of inthomycins.IMPORTANCE Streptomyces species produce numerous secondary metabolites with diverse structures and pharmacological activities that are beneficial for human health and have several applications in agriculture. In this study, hybrid nonribosomal peptide synthetase/polyketide synthase metabolites inthomycins A and B were isolated from after fermenting Streptomyces sp. SYP-A7193. Genome sequencing, gene disruption, gene complementation, heterologous expression, and activity assay revealed that the biosynthesis gene assembly line of inthomycins A and B was a 95.3-kb trans-AT type I PKS system in the strain SYP-A7193. More importantly, Itm15, a cyclodehydratase, was identified to be an oxazole ring formation enzyme required for the biosynthesis of inthomycins A and B; it is significant to discover this catalyzation reaction in the PKS/NRPS system in the field of microbiology. Our findings could provide further insights into the diversity of trans-AT type I PKS systems and the mechanism of oxazole cyclization involved in the biosynthesis of natural products.

Dataset Information

Molecular Genetic Characterization of an Anthrabenzoxocinones Gene Cluster in Streptomyces Sp. FJS31-2 for the Biosynthesis of BE-24566B and Zunyimycin Ale.

Publications

Molecular Genetic Characterization of an Anthrabenzoxocinones Gene Cluster in Streptomyces Sp. FJS31-2 for the Biosynthesis of BE-24566B and Zunyimycin Ale.

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