Identification of AstG1, A LAL Family Regulator that Positively Controls Ansatrienins Production in Streptomyces sp. XZQH13
Identification of AstG1, A LAL Family Regulator that Positively Controls Ansatrienins Production in Streptomyces sp. XZQH13
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DOI：
10.1007/s00284-015-0798-6
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发表时间：
2015-03
影响因子：
2.6
通讯作者：
Chao Xie;Jingjing Deng;Hao-Xin Wang
中科院分区：
文献类型：
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作者：
Chao Xie;Jingjing Deng;Hao-Xin Wang
安沙霉素是一组 I 型聚酮化合物，其特征在于独特的起始单元 3-氨基-5-羟基苯甲酸。该次级代谢产物家族表现出多种生物活性，其中众所周知的成员包括利福霉素、格尔德霉素和美登素。此前，我们分离出一株AHBA合酶基因阳性菌株Streptomycesp。 XZQH13含有“沉默”的安沙霉素生物合成基因簇。位于簇内的LuxR家族调节因子geneastG1的大ATP结合调节因子的组成型表达触发了生物合成基因的表达。逆转录-PCR实验表明，与野生型相比，theastG1过表达突变体中关键生物合成基因astB4、astD1和astF1的表达被诱导。这导致从突变体中分离出两种已知的安莎三烯素：羟基霉菌三烯素 A (1) 和噻嗪三烯霉素 G (2)，并通过分析质谱和核磁共振波谱数据对其进行了鉴定。这些观察结果表明astG1可能是安莎三宁生物合成的途径特异性正调节因子。
Ansamycins is a group of type I polyketides characterized by the unique starter unit 3-amino-5-hydroxybenzoic acid. This family of secondary metabolites shows diverse biological activities, well-known members of which include rifamycin, geldanamycin, and maytansine. Previously, we isolated an AHBA synthase gene-positive strainStreptomycessp. XZQH13 containing a “silent” ansamycin biosynthetic gene clusterast. The constitutive expression of the Large-ATP-binding regulators of the LuxR family regulator geneastG1located within the cluster triggered the expression of the biosynthetic genes. Reverse transcription-PCR experiments showed that the expression of the key biosynthetic genes,astB4,astD1, andastF1, was induced in theastG1overexpression mutant compared to the wild type. This led to the isolation of two known ansatrienins, hydroxymycotrienin A (1) and thiazinotrienomycin G (2), which were identified by analysis of the mass spectral and NMR spectral data, from the mutant. These observations suggest thatastG1is probably a pathway-specific positive regulator for the biosynthesis of ansatrienin.