文献类型：期刊文献

英文题名：Construction and performance of heterologous polyketide-producing K-12-and B-derived Escherichia coli

作者：Wu, J.[1,2];Boghigian, B. A.[1];Myint, M.[1];Zhang, H.[1];Zhang, S.[2];Pfeifer, B. A.[1]

机构：[1]Tufts Univ, Ctr Sci & Technol, 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

年份：2010

卷号：51

期号：2

起止页码：196

外文期刊名：LETTERS IN APPLIED MICROBIOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000279750600012)】；

基金：JW recognizes support from the China Scholarship Council. The authors also recognize support from the Summer Scholars program at Tufts University.

语种：英文

外文关键词：BL21; E; coli; heterologous; K-12; polyketide

摘要：Aims: Escherichia coli has emerged as a viable heterologous host for the production of complex, polyketide natural compounds. In this study, polyketide biosynthesis was compared between different E. coli strains for the purpose of better understanding and improving heterologous production. Methods and Results: Both B and K-12 E. coli strains were genetically modified to support heterologous polyketide biosynthesis [specifically, 6-deoxyerythronolide B (6dEB)]. Polyketide production was analysed using a helper plasmid designed to overcome rare codon usage within E. coli. Each strain was analysed for recombinant protein production, precursor consumption, by-product production, and 6dEB biosynthesis. Of the strains tested for biosynthesis, 6dEB production was greatest for E. coli B strains. When comparing biosynthetic improvements as a function of mRNA stability vs codon bias, increased 6dEB titres were observed when additional rare codon tRNA molecules were provided. Conclusions: Escherichia coli B strains and the use of tRNA supplementation led to improved 6dEB polyketide titres. Significance and Impact of the Study: Given the medicinal potential and growing field of polyketide heterologous biosynthesis, the current study provides insight into host-specific genetic backgrounds and gene expression parameters aiding polyketide production through E. coli.