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Title: Synthetic and systems biology for microbial production of commodity chemicals

The combination of synthetic and systems biology is a powerful framework to study fundamental questions in biology and produce chemicals of immediate practical application such as biofuels, polymers, or therapeutics. However, we cannot yet engineer biological systems as easily and precisely as we engineer physical systems. In this review, we describe the path from the choice of target molecule to scaling production up to commercial volumes. We present and explain some of the current challenges and gaps in our knowledge that must be overcome in order to bring our bioengineering capabilities to the level of other engineering disciplines. Challenges start at molecule selection, where a difficult balance between economic potential and biological feasibility must be struck. Pathway design and construction have recently been revolutionized by next-generation sequencing and exponentially improving DNA synthesis capabilities. Although pathway optimization can be significantly aided by enzyme expression characterization through proteomics, choosing optimal relative protein expression levels for maximum production is still the subject of heuristic, non-systematic approaches. Toxic metabolic intermediates and proteins can significantly affect production, and dynamic pathway regulation emerges as a powerful but yet immature tool to prevent it. Host engineering arises as a much needed complement to pathway engineering for highmore » bioproduct yields; and systems biology approaches such as stoichiometric modeling or growth coupling strategies are required. A final, and often underestimated, challenge is the successful scale up of processes to commercial volumes. Sustained efforts in improving reproducibility and predictability are needed for further development of bioengineering.« less
Authors:
 [1] ;  [1] ;  [1] ;  [2] ;  [1]
  1. Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division
  2. Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Univ. of California, Berkeley, CA (United States). Dept. of Chemical & Biomolecular Engineering. Dept. of Bioengineering
Publication Date:
Grant/Contract Number:
AC02-05CH11231
Type:
Accepted Manuscript
Journal Name:
npj Systems Biology and Applications
Additional Journal Information:
Journal Volume: 2; Journal Issue: 1; Journal ID: ISSN 2056-7189
Publisher:
Springer Nature
Research Org:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
Contributing Orgs:
Univ. of California, Berkeley, CA (United States)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; synthetic biology; systems biology
OSTI Identifier:
1378752

Chubukov, Victor, Mukhopadhyay, Aindrila, Petzold, Christopher J., Keasling, Jay D., and Martín, Héctor Garcia. Synthetic and systems biology for microbial production of commodity chemicals. United States: N. p., Web. doi:10.1038/npjsba.2016.9.
Chubukov, Victor, Mukhopadhyay, Aindrila, Petzold, Christopher J., Keasling, Jay D., & Martín, Héctor Garcia. Synthetic and systems biology for microbial production of commodity chemicals. United States. doi:10.1038/npjsba.2016.9.
Chubukov, Victor, Mukhopadhyay, Aindrila, Petzold, Christopher J., Keasling, Jay D., and Martín, Héctor Garcia. 2016. "Synthetic and systems biology for microbial production of commodity chemicals". United States. doi:10.1038/npjsba.2016.9. https://www.osti.gov/servlets/purl/1378752.
@article{osti_1378752,
title = {Synthetic and systems biology for microbial production of commodity chemicals},
author = {Chubukov, Victor and Mukhopadhyay, Aindrila and Petzold, Christopher J. and Keasling, Jay D. and Martín, Héctor Garcia},
abstractNote = {The combination of synthetic and systems biology is a powerful framework to study fundamental questions in biology and produce chemicals of immediate practical application such as biofuels, polymers, or therapeutics. However, we cannot yet engineer biological systems as easily and precisely as we engineer physical systems. In this review, we describe the path from the choice of target molecule to scaling production up to commercial volumes. We present and explain some of the current challenges and gaps in our knowledge that must be overcome in order to bring our bioengineering capabilities to the level of other engineering disciplines. Challenges start at molecule selection, where a difficult balance between economic potential and biological feasibility must be struck. Pathway design and construction have recently been revolutionized by next-generation sequencing and exponentially improving DNA synthesis capabilities. Although pathway optimization can be significantly aided by enzyme expression characterization through proteomics, choosing optimal relative protein expression levels for maximum production is still the subject of heuristic, non-systematic approaches. Toxic metabolic intermediates and proteins can significantly affect production, and dynamic pathway regulation emerges as a powerful but yet immature tool to prevent it. Host engineering arises as a much needed complement to pathway engineering for high bioproduct yields; and systems biology approaches such as stoichiometric modeling or growth coupling strategies are required. A final, and often underestimated, challenge is the successful scale up of processes to commercial volumes. Sustained efforts in improving reproducibility and predictability are needed for further development of bioengineering.},
doi = {10.1038/npjsba.2016.9},
journal = {npj Systems Biology and Applications},
number = 1,
volume = 2,
place = {United States},
year = {2016},
month = {4}
}

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