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Title: Xylose Assimilation Enhances Production of Isobutanol in Engineered Saccharomyces cerevisiae

Abstract

Bioconversion of xylose—the second most abundant sugar in nature—into high–value fuels and chemicals by engineered Saccharomyces cerevisiae has been a long–term goal of the metabolic engineering community. Although most efforts have heavily focused on the production of ethanol by engineered S. cerevisiae, yields and productivities of ethanol produced from xylose have remained inferior as compared to ethanol produced from glucose. However, this entrenched focus on ethanol has concealed the fact that many aspects of xylose metabolism favor the production of non–ethanol products. Through reduced overall metabolic flux, a more respiratory nature of consumption, and evading glucose signaling pathways, the bioconversion of xylose can be more amenable to redirecting flux away from ethanol towards a desired target product. In this report, we show that coupling xylose consumption via the oxidoreductive pathway with a mitochondrially–targeted isobutanol biosynthesis pathway leads to enhanced product yields and titers as compared to cultures utilizing glucose or galactose as a carbon source. Through optimization of culture conditions, we achieve 2.6 g/L of isobutanol in fed–batch flask and bioreactor fermentations. Furthermore, these results suggest that there may be synergistic benefits of coupling xylose assimilation with the production of non–ethanol value–added products.

Authors:
 [1];  [2];  [1];  [1];  [1]; ORCiD logo [1];  [3]
+ Show Author Affiliations
  1. Univ. of Illinois at Urbana-Champaign, Urbana, IL (United States)
  2. Princeton Univ., Princeton, NJ (United States)
  3. Princeton Univ., Princeton, NJ (United States); Univ. of Illinois at Urbana-Champaign, Urbana, IL (United States)
Publication Date:
Research Org.:
Center for Advanced Bioenergy and Bioproducts Innovation (CABBI), Urbana, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER)
OSTI Identifier:
1572071
Grant/Contract Number:  
SC0018420
Resource Type:
Accepted Manuscript
Journal Name:
Biotechnology and Bioengineering
Additional Journal Information:
Journal Volume: 117; Journal Issue: 2; Journal ID: ISSN 0006-3592
Publisher:
Wiley
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; branched-chain alcohols; isobutanol; metabolic engineering; Saccharomyces cerevisiae; xylose

Citation Formats

Lane, Stephan, Zhang, Yanfei, Yun, Eun Ju, Ziolkowski, Leah, Zhang, Guochang, Jin, Yong‐Su, and Avalos, José L. Xylose Assimilation Enhances Production of Isobutanol in Engineered Saccharomyces cerevisiae. United States: N. p., 2019. Web. doi:10.1002/bit.27202.
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Lane, Stephan, Zhang, Yanfei, Yun, Eun Ju, Ziolkowski, Leah, Zhang, Guochang, Jin, Yong‐Su, & Avalos, José L. Xylose Assimilation Enhances Production of Isobutanol in Engineered Saccharomyces cerevisiae. United States. https://doi.org/10.1002/bit.27202
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Lane, Stephan, Zhang, Yanfei, Yun, Eun Ju, Ziolkowski, Leah, Zhang, Guochang, Jin, Yong‐Su, and Avalos, José L. Mon . "Xylose Assimilation Enhances Production of Isobutanol in Engineered Saccharomyces cerevisiae". United States. https://doi.org/10.1002/bit.27202. https://www.osti.gov/servlets/purl/1572071.
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@article{osti_1572071,
title = {Xylose Assimilation Enhances Production of Isobutanol in Engineered Saccharomyces cerevisiae},
author = {Lane, Stephan and Zhang, Yanfei and Yun, Eun Ju and Ziolkowski, Leah and Zhang, Guochang and Jin, Yong‐Su and Avalos, José L.},
abstractNote = {Bioconversion of xylose—the second most abundant sugar in nature—into high–value fuels and chemicals by engineered Saccharomyces cerevisiae has been a long–term goal of the metabolic engineering community. Although most efforts have heavily focused on the production of ethanol by engineered S. cerevisiae, yields and productivities of ethanol produced from xylose have remained inferior as compared to ethanol produced from glucose. However, this entrenched focus on ethanol has concealed the fact that many aspects of xylose metabolism favor the production of non–ethanol products. Through reduced overall metabolic flux, a more respiratory nature of consumption, and evading glucose signaling pathways, the bioconversion of xylose can be more amenable to redirecting flux away from ethanol towards a desired target product. In this report, we show that coupling xylose consumption via the oxidoreductive pathway with a mitochondrially–targeted isobutanol biosynthesis pathway leads to enhanced product yields and titers as compared to cultures utilizing glucose or galactose as a carbon source. Through optimization of culture conditions, we achieve 2.6 g/L of isobutanol in fed–batch flask and bioreactor fermentations. Furthermore, these results suggest that there may be synergistic benefits of coupling xylose assimilation with the production of non–ethanol value–added products.},
doi = {10.1002/bit.27202},
journal = {Biotechnology and Bioengineering},
number = 2,
volume = 117,
place = {United States},
year = {2019},
month = {10}
}
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Journal Article:
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Publisher's Version of Record
https://doi.org/10.1002/bit.27202
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Cited by: 4 works
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Figures / Tables:

Figure 1 Figure 1: Metabolic pathways for bioconversion of xylose to isobutanol. Xylose reductase (XR) converts xylose to xylitol, which is then converted to xylulose by xylitol dehydrogenase (XDH). Xylulose is then phosphorylated by xylulose kinase where it enters the pentose phosphate pathway and central carbon metabolism. Plasmid pJA180, the isobutanolmore » production plasmid used in this study, overexpresses endogenous ILV2, ILV3, and ILV5 with mitochondrial-targeted Lactococcus lactis Kivd and engineered AdhARE1.« less
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Works referenced in this record:

Xylose Fermentation by Saccharomyces cerevisiae: Challenges and Prospects
journal, February 2016

  • Moysés, Danuza; Reis, Viviane; Almeida, João
  • International Journal of Molecular Sciences, Vol. 17, Issue 3
  • DOI: 10.3390/ijms17030207

Value-added biotransformation of cellulosic sugars by engineered Saccharomyces cerevisiae
journal, July 2018

Excessive by-product formation: A key contributor to low isobutanol yields of engineered Saccharomyces cerevisiae strains
journal, December 2016

Sustainability of sugarcane production in Brazil. A review
journal, February 2018

  • Bordonal, Ricardo de Oliveira; Carvalho, João Luís Nunes; Lal, Rattan
  • Agronomy for Sustainable Development, Vol. 38, Issue 2
  • DOI: 10.1007/s13593-018-0490-x

Production of fuels and chemicals from xylose by engineered Saccharomyces cerevisiae: a review and perspective
journal, May 2017

Optogenetic regulation of engineered cellular metabolism for microbial chemical production
journal, March 2018

  • Zhao, Evan M.; Zhang, Yanfei; Mehl, Justin
  • Nature, Vol. 555, Issue 7698
  • DOI: 10.1038/nature26141

Multifunctional yeast high-copy-number shuttle vectors
journal, January 1992

A mini review on renewable sources for biofuel
journal, October 2014

Glycerol: a neglected variable in metabolic processes?
journal, January 2001

  • Brisson, Diane; Vohl, Marie-Claude; St-Pierre, Julie
  • BioEssays, Vol. 23, Issue 6
  • DOI: 10.1002/bies.1073

Lactic acid production from xylose by engineered Saccharomyces cerevisiae without PDC or ADH deletion
journal, June 2015

  • Turner, Timothy L.; Zhang, Guo-Chang; Kim, Soo Rin
  • Applied Microbiology and Biotechnology, Vol. 99, Issue 19
  • DOI: 10.1007/s00253-015-6701-3

Construction of a Quadruple Auxotrophic Mutant of an Industrial Polyploid Saccharomyces cerevisiae Strain by Using RNA-Guided Cas9 Nuclease
journal, October 2014

  • Zhang, Guo-Chang; Kong, In Iok; Kim, Heejin
  • Applied and Environmental Microbiology, Vol. 80, Issue 24
  • DOI: 10.1128/AEM.02310-14

Assessing the effect of d-xylose on the sugar signaling pathways of Saccharomyces cerevisiae in strains engineered for xylose transport and assimilation
journal, January 2018

  • Osiro, Karen O.; Brink, Daniel P.; Borgström, Celina
  • FEMS Yeast Research, Vol. 18, Issue 1
  • DOI: 10.1093/femsyr/fox096

Engineered ketol-acid reductoisomerase and alcohol dehydrogenase enable anaerobic 2-methylpropan-1-ol production at theoretical yield in Escherichia coli
journal, May 2011

  • Bastian, Sabine; Liu, Xiang; Meyerowitz, Joseph T.
  • Metabolic Engineering, Vol. 13, Issue 3, p. 345-352
  • DOI: 10.1016/j.ymben.2011.02.004

Metabolic engineering and enzyme-mediated processing: A biotechnological venture towards biofuel production – A review
journal, February 2018

  • Bilal, Muhammad; Iqbal, Hafiz M. N.; Hu, Hongbo
  • Renewable and Sustainable Energy Reviews, Vol. 82
  • DOI: 10.1016/j.rser.2017.09.070

Secretion of 2,3-dihydroxyisovalerate as a limiting factor for isobutanol production in Saccharomyces cerevisiae
journal, May 2017

  • Generoso, Wesley Cardoso; Brinek, Martin; Dietz, Heiko
  • FEMS Yeast Research, Vol. 17, Issue 3
  • DOI: 10.1093/femsyr/fox029

Uncovering the role of branched-chain amino acid transaminases in Saccharomyces cerevisiae isobutanol biosynthesis
journal, November 2017

Fermentative capacity in high-cell-density fed-batch cultures of baker's yeast
journal, June 2000

Production of ethylene glycol or glycolic acid from D-xylose in Saccharomyces cerevisiae
journal, October 2017

  • Salusjärvi, Laura; Toivari, Mervi; Vehkomäki, Maija-Leena
  • Applied Microbiology and Biotechnology, Vol. 101, Issue 22
  • DOI: 10.1007/s00253-017-8547-3

Metabolic engineering of Saccharomyces cerevisiae for production of spermidine under optimal culture conditions
journal, June 2017

Exploring the xylose paradox in Saccharomyces cerevisiae through in vivo sugar signalomics of targeted deletants
journal, May 2019

  • Osiro, Karen O.; Borgström, Celina; Brink, Daniel P.
  • Microbial Cell Factories, Vol. 18, Issue 1
  • DOI: 10.1186/s12934-019-1141-x

Glycolic acid production in the engineered yeasts Saccharomyces cerevisiae and Kluyveromyces lactis
journal, January 2013

  • Koivistoinen, Outi M.; Kuivanen, Joosu; Barth, Dorothee
  • Microbial Cell Factories, Vol. 12, Issue 1
  • DOI: 10.1186/1475-2859-12-82

Xylose utilization stimulates mitochondrial production of isobutanol and 2-methyl-1-butanol in Saccharomyces cerevisiae
journal, September 2019

Systematic Identification of Conserved Metabolites in GC/MS Data for Metabolomics and Biomarker Discovery
journal, February 2007

  • Styczynski, Mark P.; Moxley, Joel F.; Tong, Lily V.
  • Analytical Chemistry, Vol. 79, Issue 3
  • DOI: 10.1021/ac0614846

Yeast vectors for the controlled expression of heterologous proteins in different genetic backgrounds
journal, April 1995

Isobutanol production from d -xylose by recombinant Saccharomyces cerevisiae
journal, January 2013

An integrated method for spectrum extraction and compound identification from gas chromatography/mass spectrometry data
journal, August 1999

GMD@CSB.DB: the Golm Metabolome Database
journal, December 2004

Improvement of d -Lactic Acid Production in Saccharomyces cerevisiae Under Acidic Conditions by Evolutionary and Rational Metabolic Engineering
journal, August 2017

  • Baek, Seung-Ho; Kwon, Eunice Y.; Bae, Sang-Jeong
  • Biotechnology Journal, Vol. 12, Issue 10
  • DOI: 10.1002/biot.201700015

Fast 100-nm resolution three-dimensional microscope reveals structural plasticity of mitochondria in live yeast
journal, March 2002

  • Egner, Alexander; Jakobs, Stefan; Hell, Stefan W.
  • Proceedings of the National Academy of Sciences, Vol. 99, Issue 6, p. 3370-3375
  • DOI: 10.1073/pnas.052545099

Strain engineering of Saccharomyces cerevisiae for enhanced xylose metabolism
journal, November 2013

Controlling Central Carbon Metabolism for Improved Pathway Yields in Saccharomyces cerevisiae
journal, November 2015

  • Tan, Sue Zanne; Manchester, Shawn; Prather, Kristala L. J.
  • ACS Synthetic Biology, Vol. 5, Issue 2
  • DOI: 10.1021/acssynbio.5b00164

Real-time monitoring of the sugar sensing in Saccharomyces cerevisiae indicates endogenous mechanisms for xylose signaling
journal, October 2016

  • Brink, Daniel P.; Borgström, Celina; Tueros, Felipe G.
  • Microbial Cell Factories, Vol. 15, Issue 1
  • DOI: 10.1186/s12934-016-0580-x

Saccharomyces cerevisiae Engineered for Xylose Metabolism Exhibits a Respiratory Response
journal, November 2004

Compartmentalization of metabolic pathways in yeast mitochondria improves the production of branched-chain alcohols
journal, February 2013

  • Avalos, José L.; Fink, Gerald R.; Stephanopoulos, Gregory
  • Nature Biotechnology, Vol. 31, Issue 4
  • DOI: 10.1038/nbt.2509

Food versus fuel: An updated and expanded evidence
journal, August 2019

Production of 3-hydroxypropionic acid from glucose and xylose by metabolically engineered Saccharomyces cerevisiae
journal, December 2015

The Warburg and Crabtree effects: On the origin of cancer cell energy metabolism and of yeast glucose repression
journal, June 2011

  • Diaz-Ruiz, Rodrigo; Rigoulet, Michel; Devin, Anne
  • Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1807, Issue 6
  • DOI: 10.1016/j.bbabio.2010.08.010

Xylose and some non-sugar carbon sources cause catabolite repression in Saccharomyces cerevisiae
journal, October 2003

Evaluation and Optimization of Metabolome Sample Preparation Methods for Saccharomyces cerevisiae
journal, January 2013

  • Kim, Sooah; Lee, Do Yup; Wohlgemuth, Gert
  • Analytical Chemistry, Vol. 85, Issue 4
  • DOI: 10.1021/ac302881e

Enhanced isoprenoid production from xylose by engineered Saccharomyces cerevisiae : Enhanced Yeast Isoprenoid Production from Xylose
journal, July 2017

  • Kwak, Suryang; Kim, Soo Rin; Xu, Haiqing
  • Biotechnology and Bioengineering, Vol. 114, Issue 11
  • DOI: 10.1002/bit.26369

GMD@CSB.DB: The Golm Metabolome Database
text, January 2005

Food Versus Fuel: An Updated and Expanded Evidence
journal, January 2017

  • Filip, Ondrej; Janda, Karel; Kristoufek, Ladislav
  • SSRN Electronic Journal
  • DOI: 10.2139/ssrn.3070704
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    Supplementary Figure 1 (p. 36)figure
    Supplementary Figure 2 (p. 37)figure
    Supplementary Figure 3 (p. 38)figure
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