Complete Biosynthesis of Erythromycin A and Designed Analogs Using E. coli as a Heterologous Host
Complete Biosynthesis of Erythromycin A and Designed Analogs Using E. coli as a Heterologous Host
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DOI：
10.1016/j.chembiol.2010.09.013
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发表时间：
2010-11-24
影响因子：
--
通讯作者：
Pfeifer, Blaine A.
中科院分区：
文献类型：
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作者：
Zhang, Haoran;Wang, Yong;Pfeifer, Blaine A.
红霉素A是一种有效的抗生素，长期以来被认为是细菌感染的治疗选择。土栖细菌多聚孢菌（acidopolyspora）从一个55 kb的基因簇中天然产生红霉素A，该基因簇由三个大的聚酮合酶基因（每个类似于10 kb）和17个负责脱氧糖生物合成、大环内酯剪裁和抗性的额外基因组成。本研究系统地将红霉素A基因簇从S. Escherraea到E.重组菌的生物合成效价可达10 mg/l。然后修改聚酮化合物的生物合成，以允许生产两种红霉素类似物。成功建立了E。大肠杆菌作为异源生产红霉素A的可行选择，更广泛地作为定向生产红霉素类似物的平台。
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.