Regulation of tylosin biosynthesis involving 'SARP-helper' activity
Regulation of tylosin biosynthesis involving 'SARP-helper' activity
复制标题
调节涉及 "SARP-助手 "活性的泰乐菌素生物合成
DOI：
10.1111/j.1365-2958.2006.05338.x
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发表时间：
2006-10-01
影响因子：
3.6
通讯作者：
Cundliffe, Eric
中科院分区：
文献类型：
--
作者：
Bate, Neil;Bignell, Dawn R. D.;Cundliffe, Eric
在tylR的调节过程中，通过阻遏物TylQ和SARP家族的激活物TylS之间的相互作用来调节草莓链霉菌中的泰乐菌素产生。后者编码泰乐菌素生物合成（tyl）基因的途径特异性激活剂。还受TylS控制的是迄今未分配的基因tylU，其产物在此显示对泰乐菌素生产是重要的。因此，tylU的靶向破坏使泰乐菌素产率降低约80%，并且用所得菌株进行的生物转化分析揭示了聚酮化合物代谢和脱氧己糖生物合成两者的缺陷。通过tylR（而不是tylS）的工程化过表达完全消除了这种缺陷，并且Western分析显示tylU破坏的菌株中TylR的水平显著降低。这些结果与TylS和TylU协同作用以促进TylR表达的模型一致，TylU（但不是TylS）对于该模型是不必要的。SARP家族的激活蛋白，如TylS，在链霉菌属中广泛存在。并且是抗生素生产的重要调节剂。他们的行动已被广泛研究，没有事先指示相关的“助手”活动，其流行率现在仍有待确定。
Tylosin production in Streptomyces fradiae is regulated via interplay between a repressor, TylQ, and an activator of the SARP family, TylS, during regulation of tylR. The latter encodes the pathway-specific activator of the tylosin-biosynthetic (tyl) genes. Also controlled by TylS is a hitherto unassigned gene, tylU, whose product is shown here to be important for tylosin production. Thus, targeted disruption of tylU reduced tylosin yields by about 80% and bioconversion analysis with the resultant strain revealed defects in both polyketide metabolism and deoxyhexose biosynthesis. Such defects were completely eliminated by engineered overexpression of tylR (but not tylS) and Western analysis revealed significantly reduced levels of TylR in the tylU-disrupted strain. These results are consistent with a model in which TylS and TylU act in concert to facilitate expression of tylR, for which TylU (but not TylS) is nonessential. Activator proteins of the SARP family, such as TylS, are widespread among Streptomyces spp. and are important regulators of antibiotic production. Their action has been widely studied with no prior indication of associated 'helper' activity, the prevalence of which now remains to be established.