Zhou Tingan, Park Young-Kyoung, Ledesma-Amaro Rodrigo
Department of Bioengineering, Imperial College Centre for Engineering Biology, Imperial College London, London SW7 2AZ, UK; Department of Natural Product Biosynthesis, Max Planck Institute for Chemical Ecology, Hans-Knöll-Straße 8, 07745 Jena, Germany.
Department of Bioengineering, Imperial College Centre for Engineering Biology, Imperial College London, London SW7 2AZ, UK; Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, 78350 Jouy-en-Josas, France.
Bioresour Technol. 2025 Nov;435:132936. doi: 10.1016/j.biortech.2025.132936. Epub 2025 Jul 3.
β-Carotene and its derivatives have been gaining huge interest due to its applications as food supplements, nutraceuticals, pharmaceuticals, pigments, etc. Owing to their high values, sustainable microbial production has been a heated research topic. Traditional production methods, such as plant extraction and chemical synthesis, face challenges in scalability, cost, and environmental impact. With advances in synthetic biology, yeast-based biosynthesis has emerged as a promising alternative. This review provides a comprehensive summary of recent progress in the metabolic engineering strategies and fermentation optimization approaches of yeast, particularly Saccharomyces cerevisiae and Yarrowia lipolytica, for the production of β-carotene and its derivatives. In contrast to previous reviews, this work emphasizes the shared biosynthetic logic underlying structurally related derivatives, classifying them into two major groups: xanthophylls (canthaxanthin, zeaxanthin, astaxanthin, and violaxanthin) and apocarotenoids (crocetin, retinol, β-ionone, β-cyclocitral, and strigolactones). Representative cases and transferable engineering/fermentation strategies are highlighted. Advantages and limitations of yeast species as production hosts are thoroughly compared, and potential strategies to improve the production are discussed. Future work may focus on broadening product diversity in different yeast hosts and enhancing biosynthetic efficiency for a more sustainable production.
β-胡萝卜素及其衍生物因其在食品补充剂、营养保健品、药物、色素等方面的应用而备受关注。由于其高价值，可持续的微生物生产一直是一个热门研究课题。传统的生产方法，如植物提取和化学合成，在可扩展性、成本和环境影响方面面临挑战。随着合成生物学的发展，基于酵母的生物合成已成为一种有前途的替代方法。本文综述了酵母，特别是酿酒酵母和解脂耶氏酵母，在生产β-胡萝卜素及其衍生物的代谢工程策略和发酵优化方法方面的最新进展。与以往的综述不同，本文强调了结构相关衍生物背后的共同生物合成逻辑，将它们分为两大类：叶黄素（角黄素、玉米黄质、虾青素和紫黄质）和类胡萝卜素（藏红花素、视黄醇、β-紫罗兰酮、β-环柠檬醛和独脚金内酯）。突出了代表性案例和可转移的工程/发酵策略。全面比较了酵母作为生产宿主的优势和局限性，并讨论了提高产量的潜在策略。未来的工作可能集中在扩大不同酵母宿主中的产品多样性，以及提高生物合成效率以实现更可持续的生产。
