Active-site residue, domain and module swaps in modular polyketide synthases

被引:102
作者
Del Vecchio, F
Petkovic, H
Kendrew, SG
Low, L
Wilkinson, B
Lill, R
Cortés, J
Rudd, BAM
Staunton, J
Leadlay, PF
机构
[1] Univ Cambridge, Dept Biochem, Cambridge CB2 1GA, England
[2] Univ Cambridge, Chem Lab, Cambridge CB2 1GA, England
[3] GlaxoSmithKline Res & Dev Ltd, Bioproc Unit, Med Res Ctr, Stevenage SG1 2NY, Herts, England
[4] Biot Technol Ltd, Cambridge CB3 0DJ, England
[5] Novacta Biosyst Ltd, John Innes Ctr, Norwich NR4 7UH, Norfolk, England
关键词
polyketide synthase; Streptomyces fradiae; tylosin; Saccharopolyspora erythraea; erythromycin; acyltransferase; docking domain;
D O I
10.1007/s10295-003-0062-0
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Sequence comparisons of multiple acyltransferase (AT) domains from modular polyketide synthases (PKSs) have highlighted a correlation between a short sequence motif and the nature of the extender unit selected. When this motif was specifically altered in the bimodular model PKS DEBS1-TE of Saccharopolyspora erythraea, the products included triketide lactones in which acetate extension units had been incorporated instead of propionate units at the predicted positions. We also describe a cassette system for convenient construction of hybrid modular PKSs based on the tylosin PKS in Streptomyces fradiae and demonstrate its use in domain and module swaps.
引用
收藏
页码:489 / 494
页数:6
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