Wuxi Translational Medicine Research Center and Jiangsu Translational Medicine Research Institute Wuxi Branch , Wuxi , Jiangsu 214122 , P. R. China.
Beijing Innovation Centre of Food Nutrition and Human Health , Beijing Technology and Business University (BTBU) , Beijing 100048 , P. R. China.
J Agric Food Chem. 2019 Aug 28;67(34):9551-9559. doi: 10.1021/acs.jafc.9b03603. Epub 2019 Aug 19.
In oleaginous micro-organisms, nitrogen limitation activates adenosine monophosphate deaminase (AMPD) and promotes lipogenesis via the inhibition of isocitrate dehydrogenase. We found that the overexpression of homologous in favored lipid synthesis over cell growth. Total fatty acid content in the recombinant strain was 15.0-34.3% higher than that in the control, even though their biomass was similar. During the early fermentation stage, the intracellular AMP level reduced by 40-60%, together with a 1.9-2.7-fold increase in citrate content compared with the control, therefore provided more precursors for fatty acid synthesis. Moreover, the decreased AMP level resulted in metabolic reprogramming, reflected by the blocked TCA cycle and reduction of amino acids, distributing more carbon to lipid synthesis pathways. By coupling the energy balance with lipogenesis, this study provides new insights into cell metabolism under nitrogen-limited conditions and targets the regulation of fatty acid accumulation in oleaginous micro-organisms.
在产油微生物中,氮限制会激活单磷酸腺苷脱氨酶 (AMPD),通过抑制异柠檬酸脱氢酶促进脂肪生成。我们发现同源物在中的过表达有利于脂肪合成而不是细胞生长。与对照相比,重组菌株的总脂肪酸含量高出 15.0-34.3%,尽管它们的生物量相似。在早期发酵阶段,细胞内 AMP 水平降低了 40-60%,与对照相比柠檬酸含量增加了 1.9-2.7 倍,因此为脂肪酸合成提供了更多的前体。此外,AMP 水平的降低导致了代谢重编程,反映在 TCA 循环受阻和氨基酸减少,将更多的碳分配到脂质合成途径中。通过将能量平衡与脂肪生成相耦合,本研究为氮限制条件下细胞代谢提供了新的见解,并针对产油微生物中脂肪酸积累的调控提供了新的靶点。