Identification and Characterization of the Cuevaene A Biosynthetic Gene Cluster in Streptomyces sp. LZ35

Authors

  • Yuhai Jiang,

    1. State Key Laboratory of Microbial Technology, School of Life Science, Shandong University, No. 27 Shanda South Road, Jinan 250100 (P. R. China)
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    • These authors contributed equally to this work.

  • Dr. Haoxin Wang,

    1. State Key Laboratory of Microbial Technology, School of Life Science, Shandong University, No. 27 Shanda South Road, Jinan 250100 (P. R. China)
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    • These authors contributed equally to this work.

  • Dr. Chunhua Lu,

    1. Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, No. 44 Wenhua West Road, Jinan, Shandong 250012 (P. R. China)
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  • Yanjiao Ding,

    1. Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, No. 44 Wenhua West Road, Jinan, Shandong 250012 (P. R. China)
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  • Dr. Yaoyao Li,

    1. Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, No. 44 Wenhua West Road, Jinan, Shandong 250012 (P. R. China)
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  • Prof. Dr. Yuemao Shen

    Corresponding author
    1. State Key Laboratory of Microbial Technology, School of Life Science, Shandong University, No. 27 Shanda South Road, Jinan 250100 (P. R. China)
    2. Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, No. 44 Wenhua West Road, Jinan, Shandong 250012 (P. R. China)
    • State Key Laboratory of Microbial Technology, School of Life Science, Shandong University, No. 27 Shanda South Road, Jinan 250100 (P. R. China)
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Abstract

Genome sequence analysis of Streptomyces sp. LZ35 has revealed a large number of secondary metabolite pathways, including one encoded in an orphan type I polyketide synthase gene cluster that contains a putative chorismatase/3-hydroxybenzoate synthase gene. Mutagenesis and comparative metabolic profiling led to the identification of cuevaene A as the metabolic product of the gene cluster, thus making it the first 3-HBA containing polyketide biosynthetic gene cluster described to date. Cuv10 was proven to be responsible for the conversion of chorismate into 3-HBA; Cuv18 is speculated to be responsible for the 6-hydroxylation of 3-HBA during polyketide chain elongation. Additionally, several pathway-specific regulatory factors that affect the production of cuevaene A were identified. Our results indicate that targeted inactivation of a gene followed by comparative metabolic profiling is a useful approach to identify and characterize cryptic biosynthetic gene clusters.

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