Engineering of Saccharomyces cerevisiae for enhanced metabolic robustness and L-lactic acid production from lignocellulosic biomass
Artikel i vetenskaplig tidskrift, 2024

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.

Lactic acidYeastXyloseSaccharomyces cerevisiaeRobustnessMetabolic engineeringMetabolic modeling


BoHyun Choi

Chalmers, Life sciences, Industriell bioteknik

Albert Tafur Rangel

Chalmers, Life sciences, Systembiologi

Novo Nordisk Fonden

Eduard Kerkhoven

Chalmers, Life sciences, Systembiologi

Novo Nordisk Fonden

Science for Life Laboratory (SciLifeLab)

Yvonne Nygård

Chalmers, Life sciences, Industriell bioteknik

Teknologian Tutkimuskeskus (VTT)

Metabolic Engineering

1096-7176 (ISSN) 1096-7184 (eISSN)

Vol. 84 23-33

Bioplaster och vaxestrar från träråvara genom samodling av bakterier och jäst

J. Gust. Richert stiftelse (2022-0073), 2023-01-01 -- 2023-12-31.

Formas (2019-02510), 2020-04-01 -- 2022-03-31.



Bioinformatik (beräkningsbiologi)



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