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

Haoran Zhang; Yong Wang; Jiequn Wu; Karin Skalina; Blaine A. Pfeifer

doi:10.1016/j.chembiol.2010.09.013

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

Haoran Zhang, Yong Wang, Jiequn Wu, Karin Skalina, Blaine A. Pfeifer

Research output: Contribution to journal › Article › peer-review

85 Scopus citations

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.

Original language	American English
Pages (from-to)	1232-1240
Number of pages	9
Journal	Chemistry and Biology
Volume	17
Issue number	11
DOIs	https://doi.org/10.1016/j.chembiol.2010.09.013
State	Published - Nov 24 2010
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmacology
Drug Discovery
Clinical Biochemistry

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10.1016/j.chembiol.2010.09.013

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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.",

author = "Haoran Zhang and Yong Wang and Jiequn Wu and Karin Skalina and Pfeifer, {Blaine A.}",

note = "Funding Information: 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.",

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doi = "10.1016/j.chembiol.2010.09.013",

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T1 - Complete biosynthesis of erythromycin A and designed analogs using E. coli as a heterologous host

AU - Zhang, Haoran

AU - Wang, Yong

AU - Wu, Jiequn

AU - Skalina, Karin

AU - Pfeifer, Blaine A.

N1 - Funding Information: 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.

PY - 2010/11/24

Y1 - 2010/11/24

N2 - 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.

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

Abstract

ASJC Scopus subject areas

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