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

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 <em>Issatchenkia orientalis</em>. 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 <em>I. orientalis</em> platform to enhance acetyl-CoA-derived citramalic acid and triacetic acid lactone production by 1.22- and 4.35-fold, respectively. Our work establishes <em>I. orientalis</em> as a versatile platform to produce markedly reduced and acetyl-CoA-derived chemicals.. Authors: Zhao, Huimin [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)] (ORCID:0000000290696739); Rabinowitz, Joshua [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)] (ORCID:0000000212474727); Guest, Jeremy [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)] (ORCID:0000000324892579); Zhu, Zhixin [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)]; Bhagwat, Sarang [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)] (ORCID:0000000226202829). DOE Contract: SC0018420. Subjects: bioproducts; metabolic engineering