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Probing the heterologous metabolism supporting 6-deoxyerythronolide B biosynthesis in Escherichia coli
Article first published online: 19 MAR 2009
DOI: 10.1111/j.1751-7915.2009.00099.x
© 2009 The Authors; Journal compilation © 2009 Society for Applied Microbiology and Blackwell Publishing Ltd
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Additional Information
How to Cite
Zhang, H., Wang, Y., Boghigian, B. and Pfeifer, B. A. (2009), Probing the heterologous metabolism supporting 6-deoxyerythronolide B biosynthesis in Escherichia coli. Microbial Biotechnology, 2: 390–394. doi: 10.1111/j.1751-7915.2009.00099.x
Publication History
- Issue published online: 17 APR 2009
- Article first published online: 19 MAR 2009
- Received 1 October, 2008; accepted 11 February, 2009.
Summary
Heterologous biosynthesis offers a new way to capture the medicinal properties presented by complex natural products. In this study, production of 6-deoxyerythronolide B (6dEB), the polyketide precursor to the antibiotic erythromycin, was used to probe the heterologous pathways needed for Escherichia coli-derived biosynthesis. More specifically, the heterologous proteins responsible for 6dEB production were varied by adjusting their respective gene dosage levels. In this way, heterologous components required for posttranslational modification, 6dEB biosynthesis, and substrate provision were adjusted in expression levels to observe the relative effect each has on final heterologous biosynthesis. The results indicate that both the biosynthetic and substrate provision heterologous proteins impact 6dEB formation to a greater extent when compared with posttranslational modification and suggest these components for future protein and metabolic engineering.