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Publication    
Bioorganic Chemistry, 2012, 44, 1-7.

Insights into fluorometabolite biosynthesis in Streptomyces cattleya DSM46488 through knockout mutants

C. Zhao, P. Li, Z. Deng, H.Y. Ou *, R.P. McGlinchey, D. O'Hagan *

 Link to PubMed
 
Streptomyces cattleya DSM 46488 is unusual in its ability to biosynthesise fluorine containing natural products, where it can produce fluoroacetate and 4-fluorothreonine. The individual enzymes involved in fluorometabolite biosynthesis have already been demonstrated in in vitro investigations. Candidate genes for the individual biosynthetic steps were located from recent genome sequences. In vivo inactivation of individual genes including those encoding the S-adenosyl-l-methionine:fluoride adenosyltransferase (fluorinase, SCATT_41540), 5'-fluoro-5'-deoxyadenosine phosphorylase (SCATT_41550), fluoroacetyl-CoA thioesterase (SCATT_41470), 5-fluoro-5-deoxyribose-1-phosphate isomerase (SCATT_20080) and a 4-fluorothreonine acetaldehyde transaldolase (SCATT_p11780) confirm that they are essential for fluorometabolite production. Notably gene disruption of the transaldolase (SCATT_p11780) resulted in a mutant which could produce fluoroacetate but was blocked in its ability to biosynthesise 4-fluorothreonine, revealing a branchpoint role for the PLP-transaldolase.

News in Chinese
基于卡特利链霉菌全基因测序的产含氟化合物合成途径解析

我组和英国圣安德鲁斯大学O’Hagan教授课题组合作,利用基因组挖掘策略和基因敲除技术成功确定了含氟化合物生物合成途径的关键酶。研究论文于2012年10月作为“Highly Important Paper”发表于Bioorganic Chemistry杂志。天然的含氟产物十分地稀有,而含氟化合物是一类在制药、农药及有机材料领域具有十分重要作用的物质。因此,近年来对于含氟化合物的生物合成机制解析引起了广泛的兴趣。该研究证实了卡特利链霉菌 (Streptomyces cattleya)中参与含氟化合物合成的关键基因散落地分布于6.2Mb的染色体和1.8Mb的巨型质粒上。
 

 

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