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Title: In-depth understanding of molecular mechanisms of aldehyde toxicity to engineer robust Saccharomyces cerevisiae

Abstract

Aldehydes are ubiquitous electrophilic compounds that ferment microorganisms including Saccharomyces cerevisiae encounter during the fermentation processes to produce food, fuels, chemicals, and pharmaceuticals. Aldehydes pose severe toxicity to the growth and metabolism of the S. cerevisiae through a variety of toxic molecular mechanisms, predominantly via damaging macromolecules and hampering the production of targeted compounds. Compounds with aldehyde functional groups are far more toxic to S. cerevisiae than all other functional classes, and toxic potency depends on physicochemical characteristics of aldehydes. The yeast synthetic biology community established a design–build–test–learn framework to develop S. cerevisiae cell factories to valorize the sustainable and renewable biomass, including the lignin-derived substrates. However, thermochemically pretreated biomass-derived substrate streams contain diverse aldehydes (e.g., glycolaldehyde and furfural), and biological conversions routes of lignocellulosic compounds consist of toxic aldehyde intermediates (e.g., formaldehyde and methylglyoxal), and some of the high-value targeted products have aldehyde functional group (e.g., vanillin and benzaldehyde). Numerous studies comprehensively characterized both single and additive effects of aldehyde toxicity via systems biology investigations, and novel molecular approaches have been discovered to overcome the aldehyde toxicity. Based on those novel approaches, researchers successfully developed synthetic yeast cell factories to convert lignocellulosic substrates to valuable products, including aldehyde compounds.more » Here, we highlight the salient relationship of physicochemical charac- teristics and molecular toxicity of aldehydes, the molecular detoxification and macromolecules protection mechanisms of aldehydes, and the advances of engineering robust S. cerevisiae against complex mixtures of aldehyde inhibitors.« less

Authors:
ORCiD logo [1]; ORCiD logo [2]
+ Show Author Affiliations
  1. Southern Illinois Univ., Carbondale, IL (United States)
  2. Univ. of Illinois at Urbana-Champaign, 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:
1807574
Grant/Contract Number:  
SC0018420
Resource Type:
Accepted Manuscript
Journal Name:
Applied Microbiology and Biotechnology
Additional Journal Information:
Journal Volume: 105; Journal Issue: 7; Journal ID: ISSN 0175-7598
Publisher:
Springer
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; S. cerevisiae; aldehydes; toxicity; detoxification; lignocellulose

Citation Formats

Jayakody, Lahiru N., and Jin, Yong-Su. In-depth understanding of molecular mechanisms of aldehyde toxicity to engineer robust Saccharomyces cerevisiae. United States: N. p., 2021. Web. doi:10.1007/s00253-021-11213-1.
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Jayakody, Lahiru N., & Jin, Yong-Su. In-depth understanding of molecular mechanisms of aldehyde toxicity to engineer robust Saccharomyces cerevisiae. United States. https://doi.org/10.1007/s00253-021-11213-1
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Jayakody, Lahiru N., and Jin, Yong-Su. Sat . "In-depth understanding of molecular mechanisms of aldehyde toxicity to engineer robust Saccharomyces cerevisiae". United States. https://doi.org/10.1007/s00253-021-11213-1. https://www.osti.gov/servlets/purl/1807574.
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@article{osti_1807574,
title = {In-depth understanding of molecular mechanisms of aldehyde toxicity to engineer robust Saccharomyces cerevisiae},
author = {Jayakody, Lahiru N. and Jin, Yong-Su},
abstractNote = {Aldehydes are ubiquitous electrophilic compounds that ferment microorganisms including Saccharomyces cerevisiae encounter during the fermentation processes to produce food, fuels, chemicals, and pharmaceuticals. Aldehydes pose severe toxicity to the growth and metabolism of the S. cerevisiae through a variety of toxic molecular mechanisms, predominantly via damaging macromolecules and hampering the production of targeted compounds. Compounds with aldehyde functional groups are far more toxic to S. cerevisiae than all other functional classes, and toxic potency depends on physicochemical characteristics of aldehydes. The yeast synthetic biology community established a design–build–test–learn framework to develop S. cerevisiae cell factories to valorize the sustainable and renewable biomass, including the lignin-derived substrates. However, thermochemically pretreated biomass-derived substrate streams contain diverse aldehydes (e.g., glycolaldehyde and furfural), and biological conversions routes of lignocellulosic compounds consist of toxic aldehyde intermediates (e.g., formaldehyde and methylglyoxal), and some of the high-value targeted products have aldehyde functional group (e.g., vanillin and benzaldehyde). Numerous studies comprehensively characterized both single and additive effects of aldehyde toxicity via systems biology investigations, and novel molecular approaches have been discovered to overcome the aldehyde toxicity. Based on those novel approaches, researchers successfully developed synthetic yeast cell factories to convert lignocellulosic substrates to valuable products, including aldehyde compounds. Here, we highlight the salient relationship of physicochemical charac- teristics and molecular toxicity of aldehydes, the molecular detoxification and macromolecules protection mechanisms of aldehydes, and the advances of engineering robust S. cerevisiae against complex mixtures of aldehyde inhibitors.},
doi = {10.1007/s00253-021-11213-1},
journal = {Applied Microbiology and Biotechnology},
number = 7,
volume = 105,
place = {United States},
year = {Sat Mar 20 00:00:00 EDT 2021},
month = {Sat Mar 20 00:00:00 EDT 2021}
}
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journal, May 2010

  • Gounaris, Y.
  • Flavour and Fragrance Journal, Vol. 25, Issue 5
  • DOI: 10.1002/ffj.1996

Glutathione and glutathione-dependent enzymes represent a co-ordinately regulated defence against oxidative stress
journal, January 1999

Production of pyruvate in Saccharomyces cerevisiae through adaptive evolution and rational cofactor metabolic engineering
journal, August 2012

Cytotoxicity Mechanism of Two Naphthoquinones (Menadione and Plumbagin) in Saccharomyces cerevisiae
journal, December 2008

Methods for Pretreatment of Lignocellulosic Biomass for Efficient Hydrolysis and Biofuel Production
journal, April 2009

  • Kumar, Parveen; Barrett, Diane M.; Delwiche, Michael J.
  • Industrial & Engineering Chemistry Research, Vol. 48, Issue 8, p. 3713-3729
  • DOI: 10.1021/ie801542g

Construction of synthetic regulatory networks in yeast
journal, February 2012

Functions of aldehyde reductases from Saccharomyces cerevisiae in detoxification of aldehyde inhibitors and their biotechnological applications
journal, October 2018

  • Wang, Hanyu; Li, Qian; Kuang, Xiaolin
  • Applied Microbiology and Biotechnology, Vol. 102, Issue 24
  • DOI: 10.1007/s00253-018-9425-3

Engineering yeast for utilization of alternative feedstocks
journal, October 2018

Production of natural products through metabolic engineering of Saccharomyces cerevisiae
journal, December 2015

Physiological responses of Pseudomonas putida to formaldehyde during detoxification: Microarrays revealed P. putida responses to toxins
journal, December 2007

Bioremediation of industrial effluents containing heavy metals using brewing cells of Saccharomyces cerevisiae as a green technology: a review
journal, December 2011

  • Soares, Eduardo V.; Soares, Helena M. V. M.
  • Environmental Science and Pollution Research, Vol. 19, Issue 4
  • DOI: 10.1007/s11356-011-0671-5

Resistance of Saccharomyces cerevisiae to High Concentrations of Furfural Is Based on NADPH-Dependent Reduction by at Least Two Oxireductases
journal, October 2009

  • Heer, D.; Heine, D.; Sauer, U.
  • Applied and Environmental Microbiology, Vol. 75, Issue 24
  • DOI: 10.1128/AEM.01649-09

Fermentation of lignocellulosic hydrolysates. II: inhibitors and mechanisms of inhibition
journal, August 2000

Mechanistic Details of Early Steps in Coenzyme Q Biosynthesis Pathway in Yeast
journal, October 2016

The molecular defences against reactive oxygen species in yeast
journal, February 1996

Stress-controlled transcription factors, stress-induced genes and stress tolerance in budding yeast
journal, October 2000

Glucosylceramide Contained in Koji Mold-Cultured Cereal Confers Membrane and Flavor Modification and Stress Tolerance to Saccharomyces cerevisiae during Coculture Fermentation
journal, March 2015

  • Sawada, Kazutaka; Sato, Tomoya; Hamajima, Hiroshi
  • Applied and Environmental Microbiology, Vol. 81, Issue 11
  • DOI: 10.1128/AEM.00454-15

Metabolic engineering of Saccharomyces cerevisiae for production of fatty acid-derived biofuels and chemicals
journal, January 2014

Treatment of the budding yeast Saccharomyces cerevisiae with the lipid peroxidation product 4-HNE provokes a temporary cell cycle arrest in G1 phase
journal, October 1998

Fermentable sugars by chemical hydrolysis of biomass
journal, March 2010

  • Binder, J. B.; Raines, R. T.
  • Proceedings of the National Academy of Sciences, Vol. 107, Issue 10, p. 4516-4521
  • DOI: 10.1073/pnas.0912073107

Model-driven generation of artificial yeast promoters
journal, April 2020

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