Rapid expansion of global market of lactic acid (LA) has prompted research towards cheaper and more eco-friendly strategies for its production. Nowadays, LA is produced mainly through fermentation of simple sugars or starchy biomass (e.g. corn) and its price is relatively high. Lignocellulose could be an advantageous alternative feedstock for LA production owing to its high abundance and low cost. However, the most effective natural producers of LA cannot directly ferment lignocellulose. So far, metabolic engineering aimed at developing microorganisms combining efficient LA production and cellulose hydrolysis has been generally based on introducing designer cellulase systems in natural LA producers. In the present study, the approach consisted in improving LA production in the natural cellulolytic bacterium Clostridium thermocellum DSM1313. The expression of the native lactate dehydrogenase was enhanced by functional replacement of its original promoter with stronger ones resulting in a 10-fold increase in specific activity, which resulted in a 2-fold increase of LA yield. It is known that eliminating allosteric regulation can also increase lactic acid production in C. thermocellum, however we were unable to insert strong promoters upstream of the de-regulated ldh gene. A strategy combining these regulations and inactivation of parasitic pathways appears essential for developing a homolactic C. thermocellum.

中文翻译：

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通过提高乳酸脱氢酶表达构建乳酸过量产热纤梭菌

乳酸 (LA) 全球市场的快速扩张促使人们研究更便宜、更环保的生产策略。目前，LA主要通过单糖或淀粉类生物质（如玉米）发酵生产，价格相对较高。由于其丰度高且成本低，木质纤维素可能是 LA 生产的一种有利的替代原料。然而，最有效的 LA 天然生产者不能直接发酵木质纤维素。迄今为止，旨在开发结合高效 LA 生产和纤维素水解的微生物的代谢工程通常基于在天然 LA 生产者中引入设计纤维素酶系统。在本研究中，该方法包括提高天然纤维素分解细菌热纤梭菌 DSM1313 中 LA 的产量。天然乳酸脱氢酶的表达通过用更强的启动子功能替换其原始启动子而增强，导致比活性增加 10 倍，从而导致 LA 产量增加 2 倍。众所周知，消除变构调节也可以增加热纤梭菌中乳酸的产生，但是我们无法在失调的 ldh 基因上游插入强启动子。将这些规定与寄生途径灭活相结合的策略似乎对于开发同型热纤梭菌至关重要。众所周知，消除变构调节也可以增加热纤梭菌中乳酸的产生，但是我们无法在失调的 ldh 基因上游插入强启动子。将这些规定与寄生途径灭活相结合的策略似乎对于开发同型热纤梭菌至关重要。众所周知，消除变构调节也可以增加热纤梭菌中乳酸的产生，但是我们无法在失调的 ldh 基因上游插入强启动子。将这些规定与寄生途径灭活相结合的策略似乎对于开发同型热纤梭菌至关重要。