論文 - 詳細
| RRC ID | 35298 |
|---|---|
| 著者 | Zhang H, Boghigian BA, Pfeifer BA. |
| タイトル | Investigating the role of native propionyl-CoA and methylmalonyl-CoA metabolism on heterologous polyketide production in Escherichia coli. |
| ジャーナル | Biotechnol Bioeng |
| Abstract |
6-Deoxyerythronolide B (6dEB) is the macrocyclic aglycone precursor of the antibiotic natural product erythromycin. Heterologous production of 6dEB in Escherichia coli was accomplished, in part, by designed over-expression of a native prpE gene (encoding a propionyl-CoA synthetase) and heterologous pcc genes (encoding a propionyl-CoA carboxylase) to supply the needed propionyl-CoA and (2S)-methylmalonyl-CoA biosynthetic substrates. Separate E. coli metabolism includes three enzymes, Sbm (a methylmalonyl-CoA mutase), YgfG (a methylmalonyl-CoA decarboxylase), and YgfH (a propionyl-CoA:succinate CoA transferase), also involved in propionyl-CoA and methylmalonyl-CoA metabolism. In this study, the sbm, ygfG, and ygfH genes were individually deleted and over-expressed to investigate their effect on heterologous 6dEB production. Our results indicate that the deletion and over-expression of sbm did not influence 6dEB production; ygfG over-expression reduced 6dEB production by fourfold while ygfH deletion increased 6dEB titers from 65 to 129 mg/L in shake flask experiments. It was also found that native E. coli metabolism could support 6dEB biosynthesis in the absence of exogenous propionate and the substrate provision pcc genes. Lastly, the effect of the ygfH deletion was tested in batch bioreactor cultures in which 6dEB titers improved from 206 to 527 mg/L. |
| 巻・号 | 105(3) |
| ページ | 567-73 |
| 公開日 | 2010-2-15 |
| DOI | 10.1002/bit.22560 |
| PMID | 19806677 |
| MeSH | Acyl Coenzyme A / metabolism* Coenzyme A-Transferases / genetics Coenzyme A-Transferases / metabolism Erythromycin / analogs & derivatives Erythromycin / metabolism Escherichia coli / metabolism* Escherichia coli Proteins / genetics Escherichia coli Proteins / metabolism Gene Deletion Gene Dosage Gene Expression Macrolides / metabolism* Methylmalonyl-CoA Decarboxylase / genetics Methylmalonyl-CoA Decarboxylase / metabolism Methylmalonyl-CoA Mutase / genetics Methylmalonyl-CoA Mutase / metabolism |
| IF | 4.002 |
| 引用数 | 41 |
| WOS 分野 | BIOTECHNOLOGY & APPLIED MICROBIOLOGY |
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