title: Generation of the natamycin analogs by gene engineering of natamycin biosynthetic genes in Streptomyces chattanoogensis L10.
abstract: The polyene antibiotic natamycin is widely used as an antifungal agent in both human therapy and the food industry. Here we obtained four natamycin analogs with high titers, including two new compounds, by engineering of six post-polyketide synthase (PKS) tailoring enzyme encoding genes in a natamycin industrial producing strain, Streptomyces chattanoogensis L10. Precise analysis of S. chattanoogensis L10 culture identified natamycin and two natamycin analogs, 4,5-deepoxy-natamycin and 4,5-deepoxy-natamycinolide. The scnD deletion mutant of S. chattanoogensis L10 did not produce natamycin but increased the titer of 4,5-deepoxy-natamycin. Inactivation of each of scnK, scnC, and scnJ in S. chattanoogensis L10 abolished natamycin production and accumulated 4,5-deepoxy-natamycinolide. Deletion of scnG in S. chattanoogensis L10 resulted in production of two new compounds, 4,5-deepoxy-12-decarboxyl-12-methyl-natamycin and its dehydration product without natamycin production. Inactivation of the ScnG-associated ferredoxin ScnF resulted in impaired production of natamycin. Bioassay of these natamycin analogs showed that three natamycin analogs remained antifungal activities. We found that homologous glycosyltransferases genes including amphDI and nysDI can partly complement the ΔscnK mutant. Our results here also support that ScnG, ScnK, and ScnD catalyze carboxylation, glycosylation, and epoxidation in turn in the natamycin biosynthetic pathway. Thus this paper provided a method to generate natamycin analogs and shed light on the natamycin biosynthetic pathway.
authors: College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China; Key Laboratory of Microbial Biochemistry and Metabolism Engineering of Zhejiang Province, Hangzhou, Zhejiang, China.
authors: Shui-Ping
authors: SP
authors: Liu
authors: College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China; Key Laboratory of Microbial Biochemistry and Metabolism Engineering of Zhejiang Province, Hangzhou, Zhejiang, China.
authors: Peng-Hui
authors: PH
authors: Yuan
authors: College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China; Key Laboratory of Microbial Biochemistry and Metabolism Engineering of Zhejiang Province, Hangzhou, Zhejiang, China.
authors: Yue-Yue
authors: YY
authors: Wang
authors: College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China; Key Laboratory of Microbial Biochemistry and Metabolism Engineering of Zhejiang Province, Hangzhou, Zhejiang, China.
authors: Xiao-Fang
authors: XF
authors: Liu
authors: College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China; Key Laboratory of Microbial Biochemistry and Metabolism Engineering of Zhejiang Province, Hangzhou, Zhejiang, China.
authors: Zhen-Xing
authors: ZX
authors: Zhou
authors: College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China; Key Laboratory of Microbial Biochemistry and Metabolism Engineering of Zhejiang Province, Hangzhou, Zhejiang, China.
authors: Qing-ting
authors: QT
authors: Bu
authors: College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China; Key Laboratory of Microbial Biochemistry and Metabolism Engineering of Zhejiang Province, Hangzhou, Zhejiang, China.
authors: Pin
authors: P
authors: Yu
authors: College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China; Key Laboratory of Microbial Biochemistry and Metabolism Engineering of Zhejiang Province, Hangzhou, Zhejiang, China.
authors: Hui
authors: H
authors: Jiang
authors: College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China; Key Laboratory of Microbial Biochemistry and Metabolism Engineering of Zhejiang Province, Hangzhou, Zhejiang, China. Electronic address: lyq@zju.edu.cn.
authors: Yong-Quan
authors: YQ
authors: Li
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D053898:Biosynthetic Pathways; D015964:Gene Expression Regulation, Bacterial; D005818:Genetic Engineering; D010866:Natamycin / Q000031:analogs & derivatives / Q000096:biosynthesis*; D048630:Polyketide Synthases / Q000235:genetics / Q000378:metabolism; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D048630:Polyketide Synthases; D010866:Natamycin
keywords: Antifungal activities; Biosynthesis; Glycosyltransferases; Natamycin analogs; Pathway