文献类型：期刊文献

英文题名：Complete Biosynthesis of Erythromycin A and Designed Analogs Using E. coli as a Heterologous Host

作者：Zhang, Haoran[1];Wang, Yong[1,2];Wu, Jiequn[1,2];Skalina, Karin[1];Pfeifer, Blaine A.[1]

机构：[1]Tufts Univ, Dept Chem & Biol Engn, Medford, MA 02155 USA;[2]E China Univ Sci & Technol, Natl Engn Res Ctr Biotechnol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2010

卷号：17

期号：11

起止页码：1232

外文期刊名：CHEMISTRY & BIOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000285405000012)】；

基金：The authors thank Brett Boghigian for critical comments during manuscript preparation, Chaitan Khosla for supplying plasmids pBP165 and pBP173, and Tufts University for financial support.

语种：英文

摘要：Erythromycin A is a potent antibiotic long-recognized as a therapeutic option for bacterial infections. The soil-dwelling bacterium Saccharopolyspora erythraea natively produces erythromycin A from a 55 kb gene cluster composed of three large polyketide synthase genes (each similar to 10 kb) and 17 additional genes responsible for deoxysugar biosynthesis, macrolide tailoring, and resistance. In this study, the erythromycin A gene cluster was systematically transferred from S. erythraea to E. coli for reconstituted biosynthesis, with titers reaching 10 mg/l. Polyketide biosynthesis was then modified to allow the production of two erythromycin analogs. Success establishes E. coli as a viable option for the heterologous production of erythromycin A and more broadly as a platform for the directed production of erythromycin analogs.