Engineering of xylose metabolic pathways in Rhodotorula toruloides for sustainable biomanufacturing.

Hyun Gi Koh, Yong-Su Jin, Christopher V Rao, Hyunjoon Oh, Suk-Chae Jung, Quanhui Ye, Sujit Sadashiv Jagtap

Journal: FEMS yeast research 2025;25():

PMID: 40498526

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Abstract

The oleaginous yeast Rhodotorula toruloides is a promising microbial cell factory for the sustainable production of biofuels and value-added chemicals from renewable carbon sources. Unlike the conventional yeast Saccharomyces cerevisiae, R. toruloides can naturally metabolize xylose, the second most abundant sugar in lignocellulosic hydrolysates. However, its native xylose metabolism is inefficient, characterized by slow xylose uptake and accumulation of D-arabitol. Moreover, despite its phenotype, research on the enzymes involved in xylose metabolism has yet to reach a consensus. Therefore, this review provides a comprehensive analysis of the non-canonical xylose metabolism in R. toruloides, focusing on the properties of key enzymes involved in xylose metabolism. Native xylose reductase and xylitol dehydrogenase exhibit broad substrate promiscuity compared to their counterparts in the xylose-fermenting Scheffersomyces stipitis. Additionally, the absence of xylulokinase expression under xylose-utilizing conditions redirects metabolism toward D-arabitol accumulation. Consequently, D-arabitol dehydrogenases and ribulokinase play essential roles in the xylose metabolism of R. toruloides. These findings highlight the fundamental differences between R. toruloides xylose metabolism and the oxidoreductase pathways observed in other xylose-fermenting yeast, providing insights for metabolic engineering strategies to improve xylose utilization and enhance bioconversion of cellulosic hydrolysates to different bioproducts by R. toruloides.

Address: Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States.; DOE Center for Advanced Bioenergy and Bioproducts Innovation, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States.; Department of Biological and Chemical Engineering, Hongik University, Sejong 30016, Republic of Korea.; Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, United States.; DOE Center for Advanced Bioenergy and Bioproducts Innovation, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States.; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States.; DOE Center for Advanced Bioenergy and Bioproducts Innovation, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States.; Department of Chemical and Biomolecular Engineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, United States.; DOE Center for Advanced Bioenergy and Bioproducts Innovation, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States.; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States.; Department of Chemical and Biomolecular Engineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, United States.; Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States.; DOE Center for Advanced Bioenergy and Bioproducts Innovation, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States.; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States.

DOI: 10.1093/femsyr/foaf029

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MeSH Terms: Xylose, Rhodotorula, Metabolic Engineering, Metabolic Networks and Pathways, Aldehyde Reductase, Fermentation, Biofuels, Sugar Alcohols