Distributing a metabolic pathway among a microbial consortium enhances production of natural products
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Author(s)
Zhou, Kang
Qiao, Kangjian
Stephanopoulos, Gregory
Edgar, Steven McBride
Date Issued
January 2015
Journal
Nature Biotechnology
Publisher
Nature Publishing Group
Citation
Zhou, Kang, Kangjian Qiao, Steven Edgar, and Gregory Stephanopoulos. “Distributing a Metabolic Pathway Among a Microbial Consortium Enhances Production of Natural Products.” Nature Biotechnology 33, no. 4 (January 5, 2015): 377–383.
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Author's final manuscript
Abstract
Metabolic engineering of microorganisms such as Escherichia coli and Saccharomyces cerevisiae to produce high-value natural metabolites is often done through functional reconstitution of long metabolic pathways. Problems arise when parts of pathways require specialized environments or compartments for optimal function. Here we solve this problem through co-culture of engineered organisms, each of which contains the part of the pathway that it is best suited to hosting. In one example, we divided the synthetic pathway for the acetylated diol paclitaxel precursor into two modules, expressed in either S. cerevisiae or E. coli, neither of which can produce the paclitaxel precursor on their own. Stable co-culture in the same bioreactor was achieved by designing a mutualistic relationship between the two species in which a metabolic intermediate produced by E. coli was used and functionalized by yeast. This synthetic consortium produced 33 mg/L oxygenated taxanes, including a monoacetylated dioxygenated taxane. The same method was also used to produce tanshinone precursors and functionalized sesquiterpenes.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
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DOI of Published Version
https://doi.org/10.1038/nbt.3095
