Identification and Characterization of the Cuevaene A Biosynthetic Gene Cluster in Streptomyces sp LZ35
Identification and Characterization of the Cuevaene A Biosynthetic Gene Cluster in Streptomyces sp LZ35
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链霉菌 LZ35 中 Cuevaene A 生物合成基因簇的鉴定和表征
DOI：
10.1002/cbic.201300316
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发表时间：
2013-08-19
期刊：
影响因子：
3.2
通讯作者：
Shen, Yuemao
中科院分区：
文献类型：
--
作者：
Jiang, Yuhai;Wang, Haoxin;Shen, Yuemao
链霉菌LZ 35的基因组序列分析揭示了大量的次级代谢途径，包括一个编码孤儿I型聚酮合酶基因簇，其中包含一个推定的分支酶/3-羟基苯甲酸合酶基因。诱变和比较代谢谱导致鉴定cuevaene A作为基因簇的代谢产物，从而使其成为迄今为止描述的第一个含有3-HBA的聚酮生物合成基因簇。Cuv 10被证明负责分支酸转化为3-HBA;推测Cuv 18负责聚酮链延长期间3-HBA的6-羟基化。此外，还鉴定了几种影响cuevaene A产生的途径特异性调节因子。我们的研究结果表明，有针对性的基因失活，然后比较代谢谱是一个有用的方法来识别和表征隐藏的生物合成基因簇。
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.