Synthetic and systems biology for microbial production of commodity chemicals

Chubukov, Victor; Mukhopadhyay, Aindrila; Petzold, Christopher J.; Keasling, Jay D.; Martín, Héctor Garcia

doi:10.1038/npjsba.2016.9

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

Journal Article · Thu Apr 07 00:00:00 EDT 2016 · npj Systems Biology and Applications

DOI:https://doi.org/10.1038/npjsba.2016.9· OSTI ID:1378752

Chubukov, Victor ^[1]; Mukhopadhyay, Aindrila ^[1]; Petzold, Christopher J. ^[1]; Keasling, Jay D. ^[2]; Martín, Héctor Garcia ^[1]

Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division
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

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.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER)

Contributing Organization:: Univ. of California, Berkeley, CA (United States)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1378752

Journal Information:: npj Systems Biology and Applications, Vol. 2, Issue 1; ISSN 2056-7189

Publisher:: Springer NatureCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 139 works

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