title: Complete biosynthesis of erythromycin A and designed analogs using E. coli as a heterologous host.
abstract: 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.
authors.affiliation: Department of Chemical & Biological Engineering, Tufts University, Medford, MA 02155, USA.
authors.forename: Haoran
authors.initials: H
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Jiequn
authors.initials: J
authors.lastname: Wu
authors.forename: Karin
authors.initials: K
authors.lastname: Skalina
authors.forename: Blaine A
authors.initials: BA
authors.lastname: Pfeifer
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D004917:Erythromycin / Q000031:analogs & derivatives / Q000096:biosynthesis*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D013058:Mass Spectrometry; D005810:Multigene Family; D010957:Plasmids / Q000378:metabolism; D048630:Polyketide Synthases / Q000235:genetics; D016930:Saccharopolyspora / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D004917:Erythromycin; D048630:Polyketide Synthases