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Accessing Nature’s diversity through metabolic engineering and synthetic biology

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Author(s)
King, Jason R
•
Edgar, Steven McBride
•
Qiao, Kangjian
•
Stephanopoulos, Gregory
Date Issued
March 2016
Journal
F1000Research
Publisher
F1000 Research Ltd
Citation
King, Jason R.; Edgar, Steven; Qiao, Kangjian and Stephanopoulos, Gregory. “Accessing Nature’s Diversity through Metabolic Engineering and Synthetic Biology.” F1000Research 5 (March2 016): 397 © 2016 King JR et al
Version
Final published version
Abstract
In this perspective, we highlight recent examples and trends in metabolic engineering and synthetic biology that demonstrate the synthetic potential of enzyme and pathway engineering for natural product discovery. In doing so, we introduce natural paradigms of secondary metabolism whereby simple carbon substrates are combined into complex molecules through “scaffold diversification”, and subsequent “derivatization” of these scaffolds is used to synthesize distinct complex natural products. We provide examples in which modern pathway engineering efforts including combinatorial biosynthesis and biological retrosynthesis can be coupled to directed enzyme evolution and rational enzyme engineering to allow access to the “privileged” chemical space of natural products in industry-proven microbes. Finally, we forecast the potential to produce natural product-like discovery platforms in biological systems that are amenable to single-step discovery, validation, and synthesis for streamlined discovery and production of biologically active agents.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Terms of Use
Creative Commons Attribution 4.0 International License
http://creativecommons.org/licenses/by/4.0/
Persistent DSpace Link
http://hdl.handle.net/1721.1/109754
DOI of Published Version
https://doi.org/10.12688/f1000research.7311.1
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