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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 = {Mon Oct 21 00:00:00 EDT 2019},
month = {Mon Oct 21 00:00:00 EDT 2019}
}
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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: 29 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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    Supplementary Figure 1 (p. 36)figure
    Supplementary Figure 2 (p. 37)figure
    Supplementary Figure 3 (p. 38)figure
    Supplementary Figure 4 (p. 39)figure
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