Engineering of Saccharomyces cerevisiae for enhanced metabolic robustness and L-lactic acid production from lignocellulosic biomass

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Choi, BoHyun,1986Chalmers tekniska högskola,Chalmers University of Technology (author)

Engineering of Saccharomyces cerevisiae for enhanced metabolic robustness and L-lactic acid production from lignocellulosic biomass

Article/chapterEnglish2024

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2024
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LIBRIS-ID:oai:research.chalmers.se:4a5abbb1-426f-4ebe-9ef1-6606ebd827a5
https://research.chalmers.se/publication/541317URI
https://doi.org/10.1016/j.ymben.2024.05.003DOI

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Language:English
Summary in:English

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Metabolic engineering for high productivity and increased robustness is needed to enable sustainable biomanufacturing of lactic acid from lignocellulosic biomass. Lactic acid is an important commodity chemical used for instance as a monomer for production of polylactic acid, a biodegradable polymer. Here, rational and model-based optimization was used to engineer a diploid, xylose fermenting Saccharomyces cerevisiae strain to produce L-lactic acid. The metabolic flux was steered towards lactic acid through the introduction of multiple lactate dehydrogenase encoding genes while deleting ERF2, GPD1, and CYB2. A production of 93 g/L of lactic acid with a yield of 0.84 g/g was achieved using xylose as the carbon source. To increase xylose utilization and reduce acetic acid synthesis, PHO13 and ALD6 were also deleted from the strain. Finally, CDC19 encoding a pyruvate kinase was overexpressed, resulting in a yield of 0.75 g lactic acid/g sugars consumed, when the substrate used was a synthetic lignocellulosic hydrolysate medium, containing hexoses, pentoses and inhibitors such as acetate and furfural. Notably, modeling also provided leads for understanding the influence of oxygen in lactic acid production. High lactic acid production from xylose, at oxygen-limitation could be explained by a reduced flux through the oxidative phosphorylation pathway. On the contrast, higher oxygen levels were beneficial for lactic acid production with the synthetic hydrolysate medium, likely as higher ATP concentrations are needed for tolerating the inhibitors therein. The work highlights the potential of S. cerevisiae for industrial production of lactic acid from lignocellulosic biomass.

Subject headings and genre

TEKNIK OCH TEKNOLOGIER Industriell bioteknik Biokemikalier hsv//swe
ENGINEERING AND TECHNOLOGY Industrial Biotechnology Biochemicals hsv//eng
NATURVETENSKAP Data- och informationsvetenskap Bioinformatik hsv//swe
NATURAL SCIENCES Computer and Information Sciences Bioinformatics hsv//eng
Lactic acidYeastXyloseSaccharomyces cerevisiaeRobustnessMetabolic engineeringMetabolic modeling

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Tafur Rangel, Albert,1992Chalmers tekniska högskola,Chalmers University of Technology,Novo Nordisk Fonden,Novo Nordisk Foundation(Swepub:cth)tafur (author)
Kerkhoven, Eduard,1985Chalmers tekniska högskola,Chalmers University of Technology,Novo Nordisk Fonden,Novo Nordisk Foundation,Science for Life Laboratory (SciLifeLab)(Swepub:cth)eduardk (author)
Nygård, Yvonne,1986Chalmers tekniska högskola,Chalmers University of Technology,Teknologian Tutkimuskeskus (VTT),Technical Research Centre of Finland (VTT)(Swepub:cth)nygardy (author)
Chalmers tekniska högskolaNovo Nordisk Fonden (creator_code:org_t)

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In:Metabolic Engineering84, s. 23-331096-71761096-7184

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