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影响油脂积累的碳代谢关键步骤及其在产油微生物中的调控。

Critical steps in carbon metabolism affecting lipid accumulation and their regulation in oleaginous microorganisms.

机构信息

Unit of Microbiology, Division of Genetics, Cell and Developmental Biology, Department of Biology, University of Patras, 26504, Patras, Greece.

Department of Genetics, Stanford University, Stanford, CA, 94305, USA.

出版信息

Appl Microbiol Biotechnol. 2018 Mar;102(6):2509-2523. doi: 10.1007/s00253-018-8813-z. Epub 2018 Feb 8.

DOI:10.1007/s00253-018-8813-z
PMID:29423634
Abstract

Oleaginous microorganisms are able to convert numerous agro-industrial and municipal wastes into storage lipids (single cell oil (SCO)) and are therefore considered as potential biofuel producers. While from an environmental and technological point of view the idea to convert waste materials into fuels is very attractive, the production cost of SCO is not currently competitive to that of conventional oils due to the low productivity of oleaginous microorganisms in combination with the high fermentation cost. Current strategies used to optimize the lipid-accumulating capacity of oleaginous microorganisms include the overexpression of genes encoding for key enzymes implicated in fatty acid and triacylglycerol synthesis, such as ATP-dependent citrate lyase, acetyl-CoA carboxylase, malic enzyme, proteins of the fatty acid synthase complex, glycerol 3-phosphate dehydrogenase and various acyltransferases, and/or the inactivation of genes encoding for enzymes implicated in storage lipid catabolism, such as lipases and acyl-CoA oxidases. Furthermore, blocking, even partially, pathways competitive to lipid biosynthesis (e.g., those involved in the accumulation of storage polysaccharide or organic acid and polyol excretion) can also increase lipid-accumulating ability in oleaginous microorganisms. Methodologies, such as adaptive laboratory evolution, can be included in existing workflows for the generation of strains with improved lipid accumulation capacity. In our opinion, efforts should be focused in the construction of strains with high carbon uptake rates and a reprogrammed coordination of the individual parts of the oleaginous machinery that maximizes carbon flux towards lipogenesis.

摘要

产油微生物能够将大量农业工业和城市废物转化为储存油脂(单细胞油(SCO)),因此被认为是有潜力的生物燃料生产者。虽然从环境和技术的角度来看,将废物转化为燃料的想法非常吸引人,但由于产油微生物的低生产力与高发酵成本相结合,SCO 的生产成本目前还没有竞争力,无法与传统油相比。目前用于优化产油微生物油脂积累能力的策略包括过表达参与脂肪酸和三酰基甘油合成的关键酶编码基因,如依赖于 ATP 的柠檬酸裂解酶、乙酰辅酶 A 羧化酶、苹果酸酶、脂肪酸合成酶复合物的蛋白质、甘油 3-磷酸脱氢酶和各种酰基转移酶,和/或失活参与储存油脂分解代谢的酶编码基因,如脂肪酶和酰基辅酶 A 氧化酶。此外,阻断甚至部分阻断与脂质生物合成竞争的途径(例如,参与储存多糖或有机酸和多元醇排泄的途径)也可以提高产油微生物的油脂积累能力。适应性实验室进化等方法可以被包含在现有的工作流程中,以生成具有改进的脂质积累能力的菌株。在我们看来,应该集中精力构建具有高碳摄取率和重新编程的产油机制各个部分的协调能力的菌株,以最大限度地将碳通量流向脂肪生成。

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