文献类型：期刊文献

英文题名：Reprogramming lipid metabolism and morphology engineering in Yarrowia lipolytica for algae-free, high-titer production of esterified astaxanthin

作者：Zhu, Mo-Han[1];Zhou, Hong-Ze[1];Liu, Zhijie[2];Zhu, Hong[3,4];Chen, Jun[1];Yang, Chen[3,4];Liu, Feng[1];Hua, Qiang[1,5]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]Hubei Univ Technol, Cooperat Innovat Ctr Ind Fermentat, Hubei Key Lab Ind Microbiol,Minist Educ, Key Lab Fermentat Engn,Minist Educ & Hubei Provinc, Wuhan 430068, Peoples R China;[3]Shanghai Jiao Tong Univ, State Key Lab Microbial Metab, Shanghai 200240, Peoples R China;[4]Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, Shanghai 200240, Peoples R China;[5]Shanghai Collaborat Innovat Ctr Biomfg Technol, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2026

卷号：532

外文期刊名：CHEMICAL ENGINEERING JOURNAL

收录：;EI(收录号：20260920149397);WOS:【SCI-EXPANDED(收录号:WOS:001705410000001)】；

基金：This work was supported by the National Key Research and Development Program of China (2023YFA0914403) , the Key Project for Synthetic Biology of Shanghai (24HC2810800) , partially supported by Open Project Funding of the Key Laboratory of Fermentation Engineering (Ministry of Education, 202409FE04) and the Shanghai Jiao Tong University Proof of Concept Program (SJTU-PoC Program, SJTU-PoC-2025) .We thank LetPub (www.letpub.com.cn) for linguistic assistance and pre-submission expert review.

语种：英文

外文关键词：Esterified astaxanthin; Diacylglycerol acyltransferase; Free astaxanthin; Yarrowia lipolytica

摘要：Astaxanthin is a potent antioxidant, and esterified astaxanthin exhibits greater stability and bioavailability, rendering it preferable for cosmetic, nutraceutical, and aquaculture applications. However, industrial supply relies largely on Haematococcus pluvialis cultivation, which requires restrictive geographic sites and climates. Here, we develop the first systematic metabolic engineering strategy for high-level, algae-free production of esterified astaxanthin in Yarrowia lipolytica. We identified Schizochytrium sp. diacylglycerol acyltransferase ScDGAT2-1 as a versatile enzyme that esterifies astaxanthin and its intermediate phoenicoxanthin while also supporting triacylglycerol synthesis. To relieve fatty acyl-CoA competition, constraining triacylglycerol formation via deletion of endogenous diacylglycerol acyltransferase gene DGA1 and phosphatidic acid phosphohydrolase gene PAH1 outperformed enhancing triacylglycerol hydrolysis by intracellular lipase gene TGL4 overexpression, increasing the esterified fraction to 39.6% of total astaxanthin. To further mitigate intermediate accumulation, we targeted ScDGAT2-1 to lipid droplets to spatially decouple astaxanthin biosynthesis from esterification, thereby raising the proportion of astaxanthin to 64% of total carotenoids. Moreover, deletion of a C2H2-type zinc finger protein Mhy1p reduced expression of the intracellular lipase genes TGL3 and TGL4 and improved fermentation performance, enabling higher and more stable esterified astaxanthin production under high-cell-density cultivation in a 5-L bioreactor. Finally, 5-L fed-batch fermentation achieved 1137.2 mg/L esterified astaxanthin and 1613.5 mg/L total astaxanthin, representing the highest heterologous titer of esterified astaxanthin reported to date. Together, these results establish a scalable yeast platform and a sustainable paradigm for industrial, algae-free manufacture of esterified astaxanthin.