文献类型：期刊文献

英文题名：De novo biosynthesis of zeaxanthin and 3-hydroxy-β-ionone by engineered Yarrowia lipolytica

作者：Chen, Xin-Liang[1];Wang, Lei[1];Wu, Ying-Ying[1];Jin, Laijiayun[1];Feng, Xin[1];Ma, Yu-Yue[1];Liu, Hao[1];Hua, Qiang[1,2];Wang, Ze-Jian[1];Wei, Liu-Jing[1]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]Shanghai Collaborat Innovat Ctr Biomfg Technol, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2025

卷号：27

期号：40

起止页码：12751

外文期刊名：GREEN CHEMISTRY

收录：;EI(收录号：20254219333315);WOS:【SCI-EXPANDED(收录号:WOS:001577472700001)】；

基金：This work was financially supported by research projects from the "Synthetic Biology" Key Technology R&D Program of Shanghai (Grant No. 25HC2820400), the Shanghai Scientific and Technological Innovation Action Plans - Scientific Instrument Development, China (Grant No. 23J21900100), and the National Natural Science Foundation of China (Grant No. 32071471). We thank Suzhou Polynovo Biotech Co., Ltd for the generous gift of non-detoxified lignocellulose hydrolysates.

语种：英文

外文关键词：Biochemistry - Cultivation - Metabolic engineering - Pigments

摘要：Zeaxanthin and its derivatives have an increasing market demand owing to their strong antioxidant, anti-cancer, and anti-inflammatory properties. Microbial biosynthesis of zeaxanthin and its derivatives serves as a sustainable and green alternative to extraction from plants and chemical synthesis. In this study, we engineered a beta-carotene-producing Yarrowia lipolytica strain by employing multi-level strategies for the efficient accumulation of zeaxanthin and 3-hydroxy-beta-ionone from its descendant. The engineered Y. lipolytica strain heterologously expressing the zeaxanthin biosynthetic pathway achieved an initial production titer of 82.36 mg L-1 in shake flask cultivation. Through systematic metabolic engineering strategies including gene copy number amplification, carbon flux redirection, pathway optimization, and cofactor balancing, the zeaxanthin titer was significantly enhanced to 729.15 mg L-1. In a controlled fed-batch bioreactor, the strain produced 2.55 g L-1 zeaxanthin, the highest reported titer to date in yeast. Furthermore, through screening carotenoid cleavage dioxygenases (CCDs), we discovered and identified an efficient pathway for the conversion of zeaxanthin to 3-hydroxy-beta-ionone. The final engineered strain produced 416.8 mg L-1 3-hydroxy-beta-ionone in shake flasks and 1.66 g L-1 in fed-batch fermentation. This is the first report of de novo biosynthesis and secretion of 3-hydroxy-beta-ionone from a recombinant organism. These results show a significant step towards demonstrating the feasibility of scaling up biologically-derived carotenoids and apocarotenoids of high value.