The gene cluster for fluorometabolite biosynthesis in Streptomyces cattleya:: A thioesterase confers resistance to fluoroacetyl-coenzyme A
The gene cluster for fluorometabolite biosynthesis in Streptomyces cattleya:: A thioesterase confers resistance to fluoroacetyl-coenzyme A
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DOI：
10.1016/j.chembiol.2006.02.014
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发表时间：
2006-05-01
影响因子：
--
通讯作者：
Spencer, Jonathan B.
中科院分区：
文献类型：
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作者：
Huang, Fanglu;Haydock, Stephen F.;Spencer, Jonathan B.
从链霉菌基因组文库中筛选出一个编码含氟代谢产物产生酶的基因簇。除了先前描述的催化由S-腺苷甲硫氨酸和氟化物形成5 '-氟-5'-脱氧腺苷的氟酶FIA之外，已经鉴定了11个其他推定的开放阅读框架。由这些基因编码的蛋白质中有三种已被鉴定。FIB被确定为该途径中的第二种酶，催化5 '-氟-5'-脱氧腺苷的磷酸解切割以产生5-氟-5-脱氧-D-核糖-1-磷酸。发现酶Fill是S-腺苷高半胱氨酸水解酶，其可用于减轻S-腺苷高半胱氨酸对氟化酶的抑制。最后，flK编码硫酯酶，该硫酯酶催化氟乙酰辅酶A而不是乙酰辅酶A的选择性分解，这表明它为生产菌株提供了对氟乙酸的抗性机制。
A genomic library of Streptomyces cattleya was screened to isolate a gene cluster encoding enzymes responsible for the production of fluorine-containing metabolites. In addition to the previously described fluorinase FIA which catalyzes the formation of 5'-fluoro-5'-deoxyadenosine from S-adenosylmethionine and fluoride, 11 other putative open reading frames have been identified. Three of the proteins encoded by these genes have been characterized. FIB was determined to be the second enzyme in the pathway, catalyzing the phosphorolytic cleavage of 5'-fluoro-5'-deoxyadenosine to produce 5-fluoro-5-deoxy-D-ribose-1-phosphate. The enzyme Fill was found to be an S-adenosylhomocysteine hydrolase, which may act to relieve S-adenosylhomocysteine inhibition of the fluorinase. Finally, flK encodes a thioesterase which catalyzes the selective breakdown of fluoroacetyl-CoA but not acetyl-CoA, suggesting that it provides the producing strain with a mechanism for resistance to fluoroacetate.