Engineering Robust Production Microbes for Large-Scale Cultivation

Maren Wehrs; Deepti Tanjore; Thomas Eng; Jeff Lievense; Todd R Pray; Aindrila Mukhopadhyay

doi:10.1016/j.tim.2019.01.006

Engineering Robust Production Microbes for Large-Scale Cultivation

Trends Microbiol. 2019 Jun;27(6):524-537. doi: 10.1016/j.tim.2019.01.006. Epub 2019 Feb 25.

Authors

Maren Wehrs¹, Deepti Tanjore², Thomas Eng³, Jeff Lievense⁴, Todd R Pray², Aindrila Mukhopadhyay⁵

Affiliations

¹ Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Institut für Genetik, Technische Universität Braunschweig, Braunschweig, Germany; Joint BioEnergy Institute, Lawrence Berkeley National Laboratory, Emeryville, CA 94608, USA.
² Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Advanced Biofuels and Bioproducts Process Development Unit, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
³ Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Joint BioEnergy Institute, Lawrence Berkeley National Laboratory, Emeryville, CA 94608, USA.
⁴ Genomatica, Inc., San Diego, CA 92121, USA.
⁵ Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Joint BioEnergy Institute, Lawrence Berkeley National Laboratory, Emeryville, CA 94608, USA; Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: amukhopadhyay@lbl.gov.

PMID: 30819548
DOI: 10.1016/j.tim.2019.01.006

Abstract

Systems biology and synthetic biology are increasingly used to examine and modulate complex biological systems. As such, many issues arising during scaling-up microbial production processes can be addressed using these approaches. We review differences between laboratory-scale cultures and larger-scale processes to provide a perspective on those strain characteristics that are especially important during scaling. Systems biology has been used to examine a range of microbial systems for their response in bioreactors to fluctuations in nutrients, dissolved gases, and other stresses. Synthetic biology has been used both to assess and modulate strain response, and to engineer strains to improve production. We discuss these approaches and tools in the context of their use in engineering robust microbes for applications in large-scale production.

Keywords: biofuel; bioproduct; bioreactor; heterogeneity; microbial hosts; mixing; scale-up; strain selection.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Review

MeSH terms

Bioengineering* / methods
Bioreactors*
Fermentation*
Genetic Association Studies
Microbiological Techniques*
Systems Biology* / methods