Data for "Decompartmentalization of the yeast mitochondrial metabolism to improve chemical production in Issatchenkia orientalis"

Zhao, Huimin; Rabinowitz, Joshua; Guest, Jeremy; Zhu, Zhixin; Bhagwat, Sarang; Li, Xi; Weilandt, Daniel; Xu, Hao; Tan, Shih-I; Tran, Vinh

doi:10.13012/B2IDB-9575028_V1

Title: Data for "Decompartmentalization of the yeast mitochondrial metabolism to improve chemical production in Issatchenkia orientalis"

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Abstract

Microbial production of chemicals may suffer from inadequate cofactor provision, a challenge further exacerbated in yeasts due to compartmentalized cofactor metabolism. Here, we perform cofactor engineering through the decompartmentalization of mitochondrial metabolism to improve succinic acid (SA) production in Issatchenkia orientalis. We localize the reducing equivalents of mitochondrial NADH to the cytosol through cytosolic expression of its pyruvate dehydrogenase (PDH) complex and couple a reductive tricarboxylic acid pathway with a glyoxylate shunt, partially bypassing an NADH-dependent malate dehydrogenase to conserve NADH. Cytosolic SA production reaches a titer of 104 g/L and a yield of 0.85 g/g glucose, surpassing the yield of 0.66 g/g glucose constrained by cytosolic NADH availability. Additionally, expressing cytosolic PDH, we expand our I. orientalis platform to enhance acetyl-CoA-derived citramalic acid and triacetic acid lactone production by 1.22- and 4.35-fold, respectively. Our work establishes I. orientalis as a versatile platform to produce markedly reduced and acetyl-CoA-derived chemicals.

Authors:

;

; Zhu, Zhixin;

; Li, Xi;

;

; Tan, Shih-I; Tran, Vinh

Department of Chemical and Biomolecular Engineering, University of Illinois Urbana-Champaign, Urbana, IL, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL, USA; Departments of Chemistry, Biochemistry, and Bioengineering, University of Illinois Urbana-Champaign, Urbana, IL, USA; Center for Advanced Bioenergy and Bioproducts Innovation (CABBI), Urbana, IL (United States)
Department of Chemistry and Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA; Center for Advanced Bioenergy and Bioproducts Innovation (CABBI), Urbana, IL (United States)
Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL, USA; The Grainger College of Engineering, Department of Civil and Environmental Engineering, University of Illinois Urbana-Champaign, Urbana, IL, USA; Center for Advanced Bioenergy and Bioproducts Innovation (CABBI), Urbana, IL (United States)
Department of Chemical and Biomolecular Engineering, University of Illinois Urbana-Champaign, Urbana, IL, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL, USA; Center for Advanced Bioenergy and Bioproducts Innovation (CABBI), Urbana, IL (United States)

Publication Date:: Fri Aug 01 20:00:00 EDT 2025

DOE Contract Number:: SC0018420

Research Org.:: Center for Advanced Bioenergy and Bioproducts Innovation (CABBI), Urbana, IL (United States); University of Illinois Urbana-Champaign

Sponsoring Org.:: U.S. Department of Energy (DOE)

Subject:: bioproducts; metabolic engineering

OSTI Identifier:: 3015501

DOI:: https://doi.org/10.13012/B2IDB-9575028_V1

Citation Formats


                    Zhao, Huimin, Rabinowitz, Joshua, Guest, Jeremy, Zhu, Zhixin, Bhagwat, Sarang, Li, Xi, Weilandt, Daniel, Xu, Hao, Tan, Shih-I, and Tran, Vinh. Data for "Decompartmentalization of the yeast mitochondrial metabolism to improve chemical production in Issatchenkia orientalis".  United States: N. p., 2025. 
        Web.  doi:10.13012/B2IDB-9575028_V1.

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                    Zhao, Huimin, Rabinowitz, Joshua, Guest, Jeremy, Zhu, Zhixin, Bhagwat, Sarang, Li, Xi, Weilandt, Daniel, Xu, Hao, Tan, Shih-I, & Tran, Vinh. Data for "Decompartmentalization of the yeast mitochondrial metabolism to improve chemical production in Issatchenkia orientalis".  United States.  doi:https://doi.org/10.13012/B2IDB-9575028_V1

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                    Zhao, Huimin, Rabinowitz, Joshua, Guest, Jeremy, Zhu, Zhixin, Bhagwat, Sarang, Li, Xi, Weilandt, Daniel, Xu, Hao, Tan, Shih-I, and Tran, Vinh. 2025.  
"Data for "Decompartmentalization of the yeast mitochondrial metabolism to improve chemical production in Issatchenkia orientalis"".  United States.  doi:https://doi.org/10.13012/B2IDB-9575028_V1.  https://www.osti.gov/servlets/purl/3015501. Pub date:Fri Aug 01 20:00:00 EDT 2025

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@article{osti_3015501,

  title        = {Data for "Decompartmentalization of the yeast mitochondrial metabolism to improve chemical production in Issatchenkia orientalis"},

  author       = {Zhao, Huimin and Rabinowitz, Joshua and Guest, Jeremy and Zhu, Zhixin and Bhagwat, Sarang and Li, Xi and Weilandt, Daniel and Xu, Hao and Tan, Shih-I and Tran, Vinh},

  abstractNote = {Microbial production of chemicals may suffer from inadequate cofactor provision, a challenge further exacerbated in yeasts due to compartmentalized cofactor metabolism. Here, we perform cofactor engineering through the decompartmentalization of mitochondrial metabolism to improve succinic acid (SA) production in Issatchenkia orientalis. We localize the reducing equivalents of mitochondrial NADH to the cytosol through cytosolic expression of its pyruvate dehydrogenase (PDH) complex and couple a reductive tricarboxylic acid pathway with a glyoxylate shunt, partially bypassing an NADH-dependent malate dehydrogenase to conserve NADH. Cytosolic SA production reaches a titer of 104 g/L and a yield of 0.85 g/g glucose, surpassing the yield of 0.66 g/g glucose constrained by cytosolic NADH availability. Additionally, expressing cytosolic PDH, we expand our I. orientalis platform to enhance acetyl-CoA-derived citramalic acid and triacetic acid lactone production by 1.22- and 4.35-fold, respectively. Our work establishes I. orientalis as a versatile platform to produce markedly reduced and acetyl-CoA-derived chemicals.},

  doi          = {10.13012/B2IDB-9575028_V1},

  journal      = {},

  number       = ,

  volume       = ,

  place        = {United States},

  year         = {Fri Aug 01 20:00:00 EDT 2025},

  month        = {Fri Aug 01 20:00:00 EDT 2025}

}

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DOI: https://doi.org/10.13012/B2IDB-9575028_V1

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