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Deletion of JEN1 and ADY2 reduces lactic acid yield from an engineered Saccharomyces cerevisiae, in xylose medium, expressing a heterologous lactate dehydrogenase.
FEMS Yeast Research ( IF 2.4 ) Pub Date : 2019-09-01 , DOI: 10.1093/femsyr/foz050
Timothy L Turner 1 , Stephan Lane 1, 2 , Lahiru N Jayakody 1 , Guo-Chang Zhang 1 , Heejin Kim 1, 2 , Whiyeon Cho 1 , Yong-Su Jin 1, 2
Affiliation  

Microorganisms have evolved to produce specific end products for many reasons, including maintaining redox balance between NAD+ and NADH. The yeast Saccharomyces cerevisiae, for example, produces ethanol as a primary end product from glucose for the regeneration of NAD+. Engineered S. cerevisiae strains have been developed to ferment lignocellulosic sugars, such as xylose, to produce lactic acid by expression of a heterologous lactate dehydrogenase (ldhA from Rhizopus oryzae) without genetic perturbation to the native ethanol pathway. Surprisingly, the engineered yeast strains predominantly produce ethanol from glucose, but produce lactic acid as the major product from xylose. Here, we provide initial evidence that the shift in product formation from ethanol to lactic acid during xylose fermentation is at least partially dependent on the presence of functioning monocarboxylate transporter genes/proteins, including JEN1 and ADY2, which are downregulated and unstable in the presence of glucose, but upregulated/stable on xylose. Future yeast metabolic engineering studies may find the feedstock/carbon selection, such as xylose, an important step toward improving the yield of target end products.

中文翻译:

在木糖培养基中,JEN1和ADY2的缺失会降低工程化酿酒酵母中表达异源乳酸脱氢酶的乳酸产量。

微生物已经进化为生产特定的最终产品,原因有很多,包括维持NAD +和NADH之间的氧化还原平衡。例如,酿酒酵母酵母从葡萄糖生产乙醇作为初级终产物,用于NAD +的再生。已经开发了工程酿酒酵母菌株以发酵木质纤维素糖,例如木糖,通过表达异源乳酸脱氢酶(来自米根霉(Rhizopus oryzae)的ldhA)来产生乳酸,而没有对天然乙醇途径的遗传干扰。令人惊讶地,工程酵母菌株主要由葡萄糖产生乙醇,但是由木糖产生乳酸作为主要产物。这里,我们提供了初步的证据,表明木糖发酵过程中从乙醇到乳酸的产物形成转变至少部分取决于功能性单羧酸盐转运蛋白基因/蛋白质(包括JEN1和ADY2)的存在,它们在葡萄糖的存在下被下调并且不稳定,但木糖上调/稳定。未来的酵母代谢工程研究可能会发现原料/碳的选择(例如木糖)是提高目标最终产品产量的重要步骤。
更新日期:2019-11-01
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