Sequencing and mutagenesis of genes from the erythromycin biosynthetic gene cluster of Saccharopolyspora erythraea that are involved in L-mycarose and D-desosamine production
Sequencing and mutagenesis of genes from the erythromycin biosynthetic gene cluster of Saccharopolyspora erythraea that are involved in L-mycarose and D-desosamine production
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DOI：
10.1099/00221287-143-10-3251
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发表时间：
1997-10-01
期刊：
影响因子：
--
通讯作者：
Katz, L
中科院分区：
文献类型：
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作者：
Summers, RG;Donadio, S;Katz, L
红霉素产生菌红多孢菌的eryA聚酮合酶基因两侧的核苷酸序列揭示了参与L-真菌糖（eryB）和D-desosamine（eryC）生物合成或附着的10个基因的存在。在这些基因中的八个中携带靶向损伤的突变菌株表明三个（eryBIV、eryBV和eryBVI）在L-真菌糖生物合成或附着中起作用，而其他五个（eryCII、eryCIII、eryCIV、eryCV和eryCVI）致力于D-desosamine生物合成或附着。基于计算机分析和早期遗传数据，其余两个基因（eryBII和eryBVII）似乎在L-真菌糖生物合成中起作用。这些基因中的三个，eryBII、eryCIII和eryCII，位于聚酮合酶基因一侧的eryAIII和eryG基因之间，而其余七个，eryBIV、eryBV、eryCVI、eryBVI、eryCIV、eryCV和eryBVII位于基因簇另一侧的eryAI基因上游。这些基因的推导产物显示出以下相似之处：己醛糖4-酮还原酶（eryBIV）、己醛酮还原酶（eryBII）、己醛糖5-差向异构酶（eryBVII）、Streptomyces peucetius的柔红霉素生物合成途径的dnmT基因（eryBVI）、糖基转移酶（eryBV和eryCIII），来自假结核耶尔森氏菌（Yersinia pseudotuberculosis，eryCIV）的AscC 3，4-淀粉酶，和哺乳动物N-甲基转移酶（eryCVI）。eryCII基因类似于细胞色素P450，但缺乏负责血红素铁协调的保守半胱氨酸残基，而eryCV基因与其他已知序列没有任何有意义的相似性。从这些和其他已知的eryB和eryC基因的预测功能，L-真菌糖和D-desosamine的生物合成途径已被推导出来。
The nucleotide sequence on both sides of the eryA polyketide synthase genes of the erythromycin-producing bacterium Saccharopolyspora erythraea reveals the presence of ten genes that are involved in L-mycarose (eryB) and D-desosamine (eryC) biosynthesis or attachment. Mutant strains carrying targeted lesions in eight of these genes indicate that three (eryBIV, eryBV and eryBVI) act in L-mycarose biosynthesis or attachment, while the other five (eryCII, eryCIII, eryCIV, eryCV and eryCVI) are devoted to D-desosamine biosynthesis or attachment. The remaining two genes (eryBII and eryBVII) appear to function in L-mycarose biosynthesis based on computer analysis and earlier genetic data. Three of these genes, eryBII, eryCIII and eryCII, lie between the eryAIII and eryG genes on one side of the polyketide synthase genes, while the remaining seven, eryBIV, eryBV, eryCVI, eryBVI, eryCIV, eryCV and eryBVII lie upstream of the eryAI gene on the other side of the gene cluster. The deduced products of these genes show similarities to: aldohexose 4-ketoreductases (eryBIV), aldoketo reductases (eryBII), aldohexose 5-epimerases (eryBVII), the dnmT gene of the daunomycin biosynthetic pathway of Streptomyces peucetius (eryBVI), glycosyltransferases (eryBV and eryCIII), the AscC 3,4-dehydratase from the ascarylose biosynthetic pathway of Yersinia pseudotuberculosis (eryCIV), and mammalian N-methyltransferases (eryCVI). The eryCII gene resembles a cytochrome P450, but lacks the conserved cysteine residue responsible for coordination of the haem iron, while the eryCV gene displays no meaningful similarity to other known sequences. From the predicted function of these and other known eryB and eryC genes, pathways for the biosynthesis of L-mycarose and D-desosamine have been deduced.