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Chem Biol. 2010 Nov 24;17(11):1232-40. doi: 10.1016/j.chembiol.2010.09.013.

Complete biosynthesis of erythromycin A and designed analogs using E. coli as a heterologous host.

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Department of Chemical & Biological Engineering, Tufts University, Medford, MA 02155, USA.


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 ~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.

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