ArticleNature communications2025
Decompartmentalization of the yeast mitochondrial metabolism to improve chemical production in Issatchenkia orientalis.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed.
- Toward engineered microbial chassis for growth-production balancing.Synthetic and systems biotechnology · 2027Review
- Engineering nonconventional yeasts to produce carboxylic acids: Advances and Prospects.Synthetic and systems biotechnology · 2027Review
- Yeast species resource exploration and application in cell factories.Synthetic and systems biotechnology · 2026Review
- Leveraging 13C-Labeling to Assign Molecular Formulas to Unknown Yeast Metabolites.Journal of the American Society for Mass Spectrometry · 2026Article
- Perspectives for Advancing Biotechnological Succinic Acid Production.Microbial biotechnology · 2026Review
- An Unorthodox Enolate-Triggered Radical Relay Directs the Chemo Upgrading of Levulinic Acid Into Citramalic Acid.ChemSusChem · 2026Article
- High yield production of 3-hydroxypropionic acid using Issatchenkia orientalis.Nature communications · 2026Article
Corrections and comments
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Authors and funding
10 authors.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.