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首页> 外文会议>Biochemical and molecular engineering XX: the next generation of biochemical engineering: from nanoscale to industrial scale >REROUTING ACETYL-COA AND NADPH TO IMPROVE LIPID AND OLEOCHEMICAL PRODUCTION IN YARROWIA LIPOLYTICA
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REROUTING ACETYL-COA AND NADPH TO IMPROVE LIPID AND OLEOCHEMICAL PRODUCTION IN YARROWIA LIPOLYTICA

机译：筛选乙酰基辅酶和NADPH以提高横纹肌脂蛋白脂和脂类的产生

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Global demand for lipid fuels and concerns about climate change have stimulated increasing efforts to produce carbon-neutral fuels directly from renewable resources. Microbially derived fatty acid fuels, the petroleum-replica fuels, have emerged as promising alternatives to meet this challenge. This is because fatty acid-based fuels offer several advantages such as high energy density, low hygroscopicity, miscibility with diesel fuels and compatibility with existing infrastructure. Recent development of the oleaginous yeast biorefinery platform has advanced the possibility to upgrade low value carbohydrates to high value fuels and oleochemicals. It is generally believed nitrogen starvation triggers lipid accumulation in oleaginous species. Under nitrogen starvation conditions, TCA metabolic activity is repressed and the overflown acetyl-CoA flux is rerouted to the fatty acid biosynthetic pathway. The central theme on this mechanism is about the acetyl-CoA supply mode: regulation of mitochondrial isocitrate dehydrogenase (ICDH). An ignored part about fatty acid biosynthesis in oleaginous yeast is the supply of NADPH, which provides the reducing equivalent to extend the carbon backbone. To overcome these challenges, we have engineered alternative cytosolic acetyl-CoA pathways to bypass the ICDH regulation, and recycled mitochondrial electrons to push the limit of lipid production in Yarrowia lipolytica. We have also been able to draw additional reducing equivalents from nitrogen metabolism and start drawing a clear picture how nitrogen starvation regulates lipogenesis in Y. lipolytica. Taken together, the reported strategy represents viable strategies to upgrade low value carbons to high value fuels and oleochemicals.
机译：全球对脂质燃料的需求以及对气候变化的担忧刺激了人们越来越多的努力，直接利用可再生资源生产碳中性燃料。微生物衍生的脂肪酸燃料（石油仿制燃料）已成为应对这一挑战的有前途的替代品。这是因为基于脂肪酸的燃料具有多种优势，例如高能量密度，低吸湿性，与柴油燃料的互溶性以及与现有基础设施的兼容性。含油酵母生物精炼平台的最新发展提高了将低价值碳水化合物升级为高价值燃料和油脂化学品的可能性。通常认为氮饥饿会引起油质物种中脂质的积累。在氮饥饿条件下，TCA代谢活性受到抑制，溢出的乙酰辅酶A流量被重新引导至脂肪酸生物合成途径。该机制的中心主题是乙酰辅酶A的供应方式：线粒体异柠檬酸脱氢酶（ICDH）的调控。关于油质酵母中脂肪酸生物合成的一个被忽略的部分是NADPH的供应，NADPH提供了还原等价物以延伸碳骨架。为了克服这些挑战，我们设计了替代性的胞质乙酰辅酶A途径来绕过ICDH调控，并回收了线粒体电子以推动解脂耶氏酵母中脂质的产生。我们还已经能够从氮代谢中得出其他还原当量，并开始清楚地了解氮饥饿如何调节解脂耶氏酵母中的脂肪生成。综上所述，所报告的策略代表了将低值碳升级为高值燃料和油脂化工的可行策略。

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