Yu Yi, Dai Jing, Yuan Quan, Liu Zihe, Tong Baisong, Shi Shuobo
Beijing Advanced Innovation Center for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.
ACS Synth Biol. 2025 Jul 18;14(7):2465-2471. doi: 10.1021/acssynbio.5c00052. Epub 2025 Jun 19.
Very long-chain fatty alcohols (VLCFOHs) are crucial components for the production of lubricants, cleaners, and cosmetics. Microbial production of these fatty alcohols has emerged as a more sustainable and potentially cost-effective alternative to traditional manufacturing methods; however, the production levels require significant optimization. Oleaginous microorganisms have received special attention for their ability to produce fatty acid derivatives due to their high lipid content. In this study, we report for the first time the expression and optimization of the biosynthetic pathway for VLCFOHs in the oleaginous yeast , targeting both the cytoplasm and peroxisome. Using the cytoplasmic pathway, 601.3 mg/L fatty alcohols and 215.9 mg/L VLCFOHs were obtained. Furthermore, two peroxisomal targeting signals were characterized and employed for VLCFOHs production. By implementing a dual-pathway approach involving both the cytoplasm and peroxisome, the fatty alcohol titer increased to 871.9 mg/L, with 320.5 mg/L VLCFOHs. In a 1-L bioreactor fed-batch fermentation, the strain expressing the dual pathway achieved titers of 5.4 g/L fatty alcohols and 2.1 g/L VLCFOHs, representing the highest reported titer of microbially produced VLCFOHs. The results expand the genetic toolboxes for and demonstrate its potential as a next-generation host to produce fatty acid derivatives.
极长链脂肪醇（VLCFOHs）是生产润滑剂、清洁剂和化妆品的关键成分。微生物生产这些脂肪醇已成为一种比传统制造方法更具可持续性且可能更具成本效益的替代方法；然而，生产水平需要大幅优化。产油微生物因其高脂质含量而具有生产脂肪酸衍生物的能力，因此受到了特别关注。在本研究中，我们首次报道了在产油酵母中针对细胞质和过氧化物酶体的VLCFOHs生物合成途径的表达和优化。使用细胞质途径，获得了601.3 mg/L的脂肪醇和215.9 mg/L的VLCFOHs。此外，还对两种过氧化物酶体靶向信号进行了表征，并用于生产VLCFOHs。通过实施涉及细胞质和过氧化物酶体的双途径方法，脂肪醇滴度提高到871.9 mg/L，VLCFOHs为320.5 mg/L。在1-L生物反应器补料分批发酵中，表达双途径的菌株实现了5.4 g/L脂肪醇和2.1 g/L VLCFOHs的滴度，这是微生物生产VLCFOHs报道的最高滴度。这些结果扩展了用于……的遗传工具箱，并证明了其作为生产脂肪酸衍生物的下一代宿主的潜力。
