Examining Organic Acid Production Potential and Growth-Coupled Strategies in Issatchenkia orientalis Using Constraint-Based Modeling

Themes: Conversion

Keywords: Metabolomics, Modeling



Illustration of production envelopes for a wild type strain and four mutant strains having different qualities of growth‐coupled production. The accessible solution space is below each curve and the production envelopes are shown stacked with each including any regions to the left. For example, the production envelope of mutant strain C encompasses the regions marked C and D, as mutant strain D is drawn on top of mutant strain C. The wild type strain produces no product at its maximum growth rate and thus has null growth coupling. Key product and growth rates used in defining qualities are indicated.

Growth-coupling product formation can facilitate strain stability by aligning industrial objectives with biological fitness. Organic acids make up many building block chemicals that can be produced from sugars obtainable from renewable biomass. Issatchenkia orientalis is a yeast strain tolerant to acidic conditions and is thus a promising host for industrial production of organic acids. Here, we use constraint-based methods to assess the potential of computationally designing growth-coupled production strains for I. orientalis that produce 22 different organic acids under aerobic or microaerobic conditions. We explore native and engineered pathways using glucose or xylose as the carbon substrates as proxy constituents of hydrolyzed biomass. We identified growth-coupled production strategies for 37 of the substrate-product pairs, with 15 pairs achieving production for any growth rate. We systematically assess the strain design solutions and categorize the underlying principles involved.


GitHub Repository — Includes metabolic model

Download (398.3 KB) includes:

  • Glucose and Xylose data
  • OK summaries
  • Heterologous and Ubiquitous Reactions

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