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Title: Industrial brewing yeast engineered for the production of primary flavor determinants in hopped beer

Flowers of the hop plant provide both bitterness and "hoppy" flavor to beer. Hops are, however, both a water and energy intensive crop and vary considerably in essential oil content, making it challenging to achieve a consistent hoppy taste in beer. Here, we report that brewer's yeast can be engineered to biosynthesize aromatic monoterpene molecules that impart hoppy flavor to beer by incorporating recombinant DNA derived from yeast, mint, and basil. Whereas metabolic engineering of biosynthetic pathways is commonly enlisted to maximize product titers, tuning expression of pathway enzymes to affect target production levels of multiple commercially important metabolites without major collateral metabolic changes represents a unique challenge. By applying state-of-the-art engineering techniques and a framework to guide iterative improvement, strains are generated with target performance characteristics. Finally, beers produced using these strains are perceived as hoppier than traditionally hopped beers by a sensory panel in a double-blind tasting.
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [1] ;  [5] ;  [6] ;  [7] ; ORCiD logo [6] ;  [5] ;  [8] ; ORCiD logo [4] ; ORCiD logo [9]
  1. Univ. of California, Berkeley, CA (United States). California Inst. of Quantitative Biosciences (QB3); Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States)
  2. Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Univ. of California, Berkeley, CA (United States). Dept. of Plant and Microbial Biology; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  3. Univ. of California, Berkeley, CA (United States). Dept. of Bioengineering
  4. Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; DOE Agile BioFoundry, Emeryville, CA (United States)
  5. Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division
  6. Univ. of California, Davis, CA (United States). Dept. of Food Science and Technology
  7. Lagunitas Brewing Company, Petaluma, CA (United States)
  8. Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Univ. of California, Berkeley, CA (United States). Dept. of Plant and Microbial Biology; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Environmental Genomics and Systems Biology Division
  9. Univ. of California, Berkeley, CA (United States). California Inst. of Quantitative Biosciences (QB3); 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 Bioengineering; Univ. of California, Berkeley, CA (United States). Dept. of Chemical and Biomolecular Engineering; Technical Univ. of Denmark, Hellerup (Denmark). Novo Nordisk Foundation Center for Sustainability
Publication Date:
Grant/Contract Number:
AC02-05CH11231; 1722376
Type:
Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 9; Journal Issue: 1; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
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)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES
OSTI Identifier:
1457017

Denby, Charles M., Li, Rachel A., Vu, Van T., Costello, Zak, Lin, Weiyin, Chan, Leanne Jade G., Williams, Joseph, Donaldson, Bryan, Bamforth, Charles W., Petzold, Christopher J., Scheller, Henrik V., Martin, Hector Garcia, and Keasling, Jay D.. Industrial brewing yeast engineered for the production of primary flavor determinants in hopped beer. United States: N. p., Web. doi:10.1038/s41467-018-03293-x.
Denby, Charles M., Li, Rachel A., Vu, Van T., Costello, Zak, Lin, Weiyin, Chan, Leanne Jade G., Williams, Joseph, Donaldson, Bryan, Bamforth, Charles W., Petzold, Christopher J., Scheller, Henrik V., Martin, Hector Garcia, & Keasling, Jay D.. Industrial brewing yeast engineered for the production of primary flavor determinants in hopped beer. United States. doi:10.1038/s41467-018-03293-x.
Denby, Charles M., Li, Rachel A., Vu, Van T., Costello, Zak, Lin, Weiyin, Chan, Leanne Jade G., Williams, Joseph, Donaldson, Bryan, Bamforth, Charles W., Petzold, Christopher J., Scheller, Henrik V., Martin, Hector Garcia, and Keasling, Jay D.. 2018. "Industrial brewing yeast engineered for the production of primary flavor determinants in hopped beer". United States. doi:10.1038/s41467-018-03293-x. https://www.osti.gov/servlets/purl/1457017.
@article{osti_1457017,
title = {Industrial brewing yeast engineered for the production of primary flavor determinants in hopped beer},
author = {Denby, Charles M. and Li, Rachel A. and Vu, Van T. and Costello, Zak and Lin, Weiyin and Chan, Leanne Jade G. and Williams, Joseph and Donaldson, Bryan and Bamforth, Charles W. and Petzold, Christopher J. and Scheller, Henrik V. and Martin, Hector Garcia and Keasling, Jay D.},
abstractNote = {Flowers of the hop plant provide both bitterness and "hoppy" flavor to beer. Hops are, however, both a water and energy intensive crop and vary considerably in essential oil content, making it challenging to achieve a consistent hoppy taste in beer. Here, we report that brewer's yeast can be engineered to biosynthesize aromatic monoterpene molecules that impart hoppy flavor to beer by incorporating recombinant DNA derived from yeast, mint, and basil. Whereas metabolic engineering of biosynthetic pathways is commonly enlisted to maximize product titers, tuning expression of pathway enzymes to affect target production levels of multiple commercially important metabolites without major collateral metabolic changes represents a unique challenge. By applying state-of-the-art engineering techniques and a framework to guide iterative improvement, strains are generated with target performance characteristics. Finally, beers produced using these strains are perceived as hoppier than traditionally hopped beers by a sensory panel in a double-blind tasting.},
doi = {10.1038/s41467-018-03293-x},
journal = {Nature Communications},
number = 1,
volume = 9,
place = {United States},
year = {2018},
month = {3}
}

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