Department of Chemical Engineering, The Pennsylvania State University, University Park, Pennsylvania, USA.
Center for Advanced Bioenergy and Bioproducts Innovation, The Pennsylvania State University, University Park, Pennsylvania, USA.
Biotechnol Prog. 2022 Sep;38(5):e3276. doi: 10.1002/btpr.3276. Epub 2022 Jun 28.
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.
生长偶联产物的形成可以通过将工业目标与生物适应性相协调来促进菌株的稳定性。有机酸是许多构建块化学品的组成部分，可以从可再生生物质中获得的糖中生产出来。东方伊萨酵母（Issatchenkia orientalis）是一种耐受酸性条件的酵母菌株，因此是工业生产有机酸的有前途的宿主。在这里，我们使用基于约束的方法来评估在有氧或微氧条件下，通过计算设计生产 22 种不同有机酸的东方伊萨酵母的生长偶联生产菌株的潜力。我们使用葡萄糖或木糖作为碳底物来探索天然和工程化途径，作为水解生物质的代表性成分。我们确定了 37 对底物-产物对的生长偶联生产策略，其中 15 对在任何生长速率下都能实现生产。我们系统地评估了菌株设计方案，并对所涉及的基本原则进行了分类。
