Xiao Kang, Yue Xiu-Hong, Chen Wen-Chao, Zhou Xue-Rong, Wang Lian, Xu Lin, Huang Feng-Hong, Wan Xia
Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences, Wuhan, China.
Key Laboratory of Biology and Genetic Improvement of Oil Crops, Ministry of Agriculture, Wuhan, China.
Front Microbiol. 2018 Feb 7;9:139. doi: 10.3389/fmicb.2018.00139. eCollection 2018.
Medium chain hydroxy fatty acids (HFAs) at ω-1, 2, or 3 positions (ω-1/2/3) are rare in nature but are attractive due to their potential applications in industry. They can be metabolically engineered in , however, the current yield is low. In this study, metabolic engineering with P450 monooxygenase was applied to regulate both the chain length and sub-terminal position of HFA products in , leading to increased yield. Five acyl-acyl carrier protein thioesterases from plants and bacteria were first evaluated for regulating the chain length of fatty acids. Co-expression of the selected thioesterase gene with a fatty acid metabolism regulator and monooxygenase boosted the production of HFAs especially ω-3-OH-C14:1, in both the wild type and deficient strain. Supplementing renewable glycerol to reduce the usage of glucose as a carbon source further increased the HFAs production to 144 mg/L, representing the highest titer of such HFAs obtained in under the comparable conditions. This study illustrated an improved metabolic strategy for medium chain ω-1/2/3 HFAs production in . In addition, the produced HFAs were mostly secreted into culture media, which eased its recovery.
ω-1、2或3位的中链羟基脂肪酸（HFAs）在自然界中很少见，但因其在工业上的潜在应用而具有吸引力。它们可以通过代谢工程生产，然而，目前的产量较低。在本研究中，应用细胞色素P450单加氧酶进行代谢工程，以调节酿酒酵母中HFA产物的链长和亚末端位置，从而提高产量。首先评估了来自植物和细菌的五种酰基-酰基载体蛋白硫酯酶对脂肪酸链长的调节作用。将所选硫酯酶基因与脂肪酸代谢调节因子和单加氧酶共表达，提高了野生型和缺陷型菌株中HFAs的产量，尤其是ω-3-OH-C14:1。补充可再生甘油以减少葡萄糖作为碳源的使用，进一步将HFAs产量提高到144 mg/L，这是在可比条件下酿酒酵母中获得的此类HFAs的最高滴度。本研究阐述了一种改进的酿酒酵母中链ω-1/2/3 HFAs生产的代谢策略。此外，产生的HFAs大多分泌到培养基中，这便于其回收。
