STEREOSPECIFIC ACYL TRANSFERS ON THE ERYTHROMYCIN-PRODUCING POLYKETIDE SYNTHASE

被引:150
作者
MARSDEN, AFA
CAFFREY, P
APARICIO, JF
LOUGHRAN, MS
STAUNTON, J
LEADLAY, PF
机构
[1] UNIV CAMBRIDGE,CAMBRIDGE CTR MOLEC RECOGNIT,CAMBRIDGE CB2 1QW,ENGLAND
[2] UNIV CAMBRIDGE,DEPT BIOCHEM,CAMBRIDGE CB2 1QW,ENGLAND
[3] UNIV CAMBRIDGE,CAMBRIDGE CTR MOLEC RECOGNIT,CAMBRIDGE CB2 1EW,ENGLAND
[4] UNIV CAMBRIDGE,CHEM LAB,DEPT ORGAN CHEM,CAMBRIDGE CB2 1EW,ENGLAND
关键词
D O I
10.1126/science.8278811
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
During assembly of complex polyketide antibiotics like erythromycin A, molecular recognition by the multienzyme polyketide synthase controls the stereochemical outcome as each successive methylmalonyl-coenzyme A (CoA) extender unit is added. Acylation of the purified erythromycin-producing polyketide synthase has shown that all six acyltransferase domains have identical stereospecificity for their normal substrate (2S)-methylmalonyl-CoA. In contrast, the configuration of the methyl-branched centers in the products, that are derived from (2S)-methylmalonyl-CoA, is different. Stereoselection during the chain building process must, therefore, involve additional epimerization steps.
引用
收藏
页码:378 / 380
页数:3
相关论文
共 27 条