Multiplex Navigation of Global Regulatory Networks (MINR) in yeast for Improved Ethanol Tolerance and Production

Liu, Rongming; Liang, Liya; Choudhury, Alaksh; Garst, Andrew D.; Eckert, Carrie A.; Oh, Eun Joong; Winkler, James; Gill, Ryan T.

doi:10.1016/j.ymben.2018.07.007

Title: Multiplex Navigation of Global Regulatory Networks (MINR) in yeast for Improved Ethanol Tolerance and Production

Journal Article · 17 July 2018 · Metabolic Engineering

DOI: https://doi.org/10.1016/j.ymben.2018.07.007 · OSTI ID:1465647

Liu, Rongming ^[1]; Liang, Liya ^[1]; Choudhury, Alaksh ^[1]; Garst, Andrew D. ^[1]; Eckert, Carrie A. ^[2]; Oh, Eun Joong ^[1]; Winkler, James ^[1]; Gill, Ryan T. ^[1]

Univ. of Colorado, Boulder, CO (United States)
Univ. of Colorado, Boulder, CO (United States); National Renewable Energy Lab. (NREL), Golden, CO (United States)

Multiplex navigation of global regulatory networks (MINR) is an approach for combinatorially reprogramming gene expression to manipulate complex phenotypes. We designed, constructed, and mapped MINR libraries containing 43,020 specific mutations in 25 regulatory genes expected to perturb the yeast regulatory network. We selected growth competition experiments for library mutants conferring increased ethanol and/or glucose tolerance. We identified specific mutants that not only possessed improved ethanol and/or glucose tolerance but also produced ethanol at concentrations up to 2-fold higher than those produced by the wild-type strain. We further determined that mutations increasing ethanol tolerance were transferable to a diploid industrial yeast strain. The facile construction and mapping of 43,020 designer regulatory mutations provide a roadmap for how to access and engineer complex phenotypes in future synthetic biology and broader efforts.

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Research Organization:: National Renewable Energy Laboratory (NREL), Golden, CO (United States)

Sponsoring Organization:: USDOE Office of Energy Efficiency and Renewable Energy (EERE), Office of Sustainable Transportation and Fuels. Bioenergy Technologies Office (BETO)

Grant/Contract Number:: AC36-08GO28308

OSTI ID:: 1465647

Report Number(s):: NREL/JA-2700-72224

Journal Information:: Metabolic Engineering, Vol. 51; ISSN 1096-7176

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 22 works

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Title: Multiplex Navigation of Global Regulatory Networks (MINR) in yeast for Improved Ethanol Tolerance and Production

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