Wang Kaifeng, Shi Tian-Qiong, Wang Jinpeng, Wei Ping, Ledesma-Amaro Rodrigo, Ji Xiao-Jun
State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, No. 30 South Puzhu Road, Nanjing 211816, People's Republic of China.
School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, No. 1 Wenyuan Road, Nanjing 210046, People's Republic of China.
ACS Synth Biol. 2022 Apr 15;11(4):1542-1554. doi: 10.1021/acssynbio.1c00613. Epub 2022 Mar 20.
Oleic acid is widely applied in the chemical, material, nutritional, and pharmaceutical industries. However, the current production of oleic acid via high oleic plant oils is limited by the long growth cycle and climatic constraints. Moreover, the global demand for high oleic plant oils, especially the palm oil, has emerged as the driver of tropical deforestation causing tropical rainforest destruction, climate change, and biodiversity loss. In the present study, an alternative and sustainable strategy for high oleic oil production was established by reprogramming the metabolism of the oleaginous yeast using a two-layer "push-pull-block" strategy. Specifically, the fatty acid synthesis pathway was first engineered to increase oleic acid proportion by altering the fatty acid profiles. Then, the content of storage oils containing oleic acid was boosted by engineering the synthesis and degradation pathways of triacylglycerides. The strain resulting from this two-layer engineering strategy produced the highest titer of high oleic microbial oil reaching 56 g/L with 84% oleic acid in fed-batch fermentation, representing a remarkable improvement of a 110-fold oil titer and 2.24-fold oleic acid proportion compared with the starting strain. This alternative and sustainable method for high oleic oil production shows the potential of substitute planting.
油酸广泛应用于化工、材料、营养和制药行业。然而，目前通过高油酸植物油生产油酸受到生长周期长和气候限制。此外，全球对高油酸植物油，尤其是棕榈油的需求已成为导致热带雨林破坏、气候变化和生物多样性丧失的热带森林砍伐的驱动因素。在本研究中，通过使用两层“推-拉-阻”策略对产油酵母的代谢进行重新编程，建立了一种替代的可持续高油酸油生产策略。具体而言，首先通过改变脂肪酸谱来改造脂肪酸合成途径，以增加油酸比例。然后，通过改造三酰甘油的合成和降解途径来提高含油酸储存油的含量。这种两层工程策略产生的菌株在补料分批发酵中产生了最高滴度的高油酸微生物油，达到56 g/L，油酸含量为84%，与起始菌株相比，油滴度提高了110倍，油酸比例提高了2.24倍，显著改善。这种替代的可持续高油酸油生产方法显示了替代种植的潜力。
