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DE-SC0019093: Establishing the thermotolerant yeast Kluyveromyces marxianus as a host for biobased fuels and chemicals production

Award Status: Active
  • Institution: The Regents of the University of California, Riverside, Riverside, CA
  • DUNS: 627797426
  • PM: Adin, Dawn
  • Most Recent Award Date: 08/15/2018
  • Number of Support Periods: 1
  • PI: Wheeldon, Ian
  • Current Budget Period: 09/15/2018 - 09/14/2019
  • Current Project Period: 09/15/2018 - 09/14/2021
  • Supplement Budget Period: N/A
 

Public Abstract

This systems and synthetic biology project seeks to understand and engineer the native phenotypes of the thermotolerant yeast Kluyveromyces marxianus. Genome-wide mutagenesis and regulation strategies will be used to investigate the genetic basis of its fast growth kinetics at temperatures upward of 48°C, high tolerance to low pH culture, and native ability to metabolize a range of hexose and pentose sugars. Functional genetic screens will identify essential genes and the genotype-phenotype relationships underpinning the native traits that make K. marxianus well-suited to industrial biotechnology. The new systems-level data created in these experiments will inform metabolic engineering strategies to increase the yield of metabolized sugars to the central chemical building block acetyl-CoA and enhance the production of biobased fuels, chemicals, and their precursors. The proposed genetic screens and biosynthesis pathway engineering will be enabled by newly developed CRISPR-based genome editing and regulation tools. The research of this project works towards strengthening a critical area of the US industrial biotechnology sector. The conversion of biomass-derived sugars and other renewable feedstocks to industrial chemicals helps create more than 100 billion dollars in revenues in the US alone. The work here develops a robust chemical biosynthesis host that is genetically accessible and can grow under harsh conditions while metabolizing a range of carbon sources, traits suited to the next generation of chemical and fuel bioprocessing.This systems and synthetic biology project seeks to understand and engineer the native phenotypes of the thermotolerant yeast Kluyveromyces marxianus. Genome-wide mutagenesis and regulation strategies will be used to investigate the genetic basis of its fast growth kinetics at temperatures upward of 48 °C, high tolerance to low pH culture, and native ability to metabolize a range of hexose and pentose sugars. Functional genetic screens will identify essential genes and the genotype-phenotype relationships underpinning the native traits that make K. marxianus well-suited to industrial biotechnology. The new systems-level data created in these experiments will inform metabolic engineering strategies to increase the yield of metabolized sugars to the central chemical building block acetyl-CoA and enhance the production of biobased fuels, chemicals, and their precursors. The proposed genetic screens and biosynthesis pathway engineering will be enabled by newly developed CRISPR-based genome editing and regulation tools. The research of this project works towards strengthening a critical area of the US industrial biotechnology sector. The conversion of biomass-derived sugars and other renewable feedstocks to industrial chemicals helps create more than 100 billion dollars in revenues in the US alone. The work here develops a robust chemical biosynthesis host that is genetically accessible and can grow under harsh conditions while metabolizing a range of carbon sources, traits suited to the next generation of chemical and fuel bioprocessing.


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