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  • Title: Identification and characterization of the cuevaene A biosynthetic gene cluster in streptomyces sp. LZ35.
    Author: Jiang Y, Wang H, Lu C, Ding Y, Li Y, Shen Y.
    Journal: Chembiochem; 2013 Aug 19; 14(12):1468-75. PubMed ID: 23824670.
    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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