Fouces Roberto, Mellado Encarnación, Díez Bruno, Barredo José Luis
Microbiology (Reading). 1999 Apr;145 ( Pt 4):855-868. doi: 10.1099/13500872-145-4-855.
The genetic organization of the left edge (tyIEDHFJ region) of the tylosin biosynthetic gene cluster from Streptomyces fradiae has been determined. Sequence analysis of a 12.9 kb region has revealed the presence of 11 ORFs, 10 of them belonging to the biosynthetic cluster. The putative functions of the proteins encoded by these genes are as follows: peptidase (ORF1, ddcA), tylosin resistance determinant (ORF2, tlrB), glycosyltransferase (ORF3, tylN), methyltransferase (ORF4, tylE), ketoreductase (ORF5, tylD), ferredoxin (ORF6, tylH2), cytochrome P450 (ORF7, tylH1), methyltransferase (ORF8, tylF), epimerase (ORF9, tylJ), acyl-CoA oxidase (ORF10, tylP) and receptor of regulatory factors (ORF11, tylQ). The functional identification of the genes in the proposed tylosin biosynthetic pathway has been deduced by database searches and previous genetic complementation studies performed with tylosin idiotrophic mutants blocked at various stages in tylosin biosynthesis. The tlrB gene has been shown to be useful as a tylosin resistance marker in Streptomyces lividans, Streptomyces parvulus and Streptomyces coelicolor and the effect of tylF on macrocin depletion has been confirmed. A pathway for the biosynthesis of 6-deoxy-D-allose, the unmethylated mycinose precursor, involving the genes tylD, tylJ and tylN is proposed.
已确定来自弗氏链霉菌的泰乐菌素生物合成基因簇左边缘（tyIEDHFJ区域）的遗传组织。对一个12.9 kb区域的序列分析揭示了11个开放阅读框（ORF）的存在，其中10个属于生物合成簇。这些基因编码的蛋白质的推定功能如下：肽酶（ORF1，ddcA）、泰乐菌素抗性决定因子（ORF2，tlrB）、糖基转移酶（ORF3，tylN）、甲基转移酶（ORF4，tylE）、酮还原酶（ORF5，tylD）、铁氧化还原蛋白（ORF6，tylH2）、细胞色素P450（ORF7，tylH1）、甲基转移酶（ORF8，tylF）、差向异构酶（ORF9，tylJ）、酰基辅酶A氧化酶（ORF10，tylP）和调节因子受体（ORF11，tylQ）。通过数据库搜索以及先前对在泰乐菌素生物合成不同阶段受阻的泰乐菌素营养缺陷型突变体进行的遗传互补研究，推断出了拟议的泰乐菌素生物合成途径中各基因的功能鉴定。已证明tlrB基因在淡紫链霉菌、小链霉菌和天蓝色链霉菌中可用作泰乐菌素抗性标记，并且已证实tylF对大环菌素消耗的影响。提出了一条由tylD、tylJ和tylN基因参与的6-脱氧-D-阿洛糖（未甲基化的霉糖前体）生物合成途径。
