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

被引：89
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
来源：
CHEMISTRY & BIOLOGY | 2010年 / 17卷 / 11期
关键词：
POLYKETIDE SYNTHASE; SACCHAROPOLYSPORA-ERYTHRAEA; ESCHERICHIA-COLI; GENE-CLUSTER; EXPRESSION; POTENT; 6-DEOXYERYTHRONOLIDE-B; ANTIBIOTICS; SPECIFICITY; RESISTANT;
D O I：
10.1016/j.chembiol.2010.09.013
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
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.
引用
收藏
页码：1232 / 1240
页数：9
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