Bubphasawan Suriyaporn, Sansatchanon Kitisak, Promdonkoy Peerada, Watcharawipas Akaraphol, Tanapongpipat Sutipa, Khamwachirapithak Peerapat, Runguphan Weerawat, Kocharin Kanokarn
Industrial Bioprocess Innovation Group, The Eastern Economic Corridor of Innovation, National Science and Technology Development Agency (NSTDA), 333 EECi Headquarters Wang Chan, Rayong, 21210, Thailand.
National Center for Genetic Engineering and Biotechnology, 113 Thailand Science Park, Paholyothin Road, Klong 1, Klong Luang, 12120, Pathumthani, Thailand.
Bioresour Bioprocess. 2025 Sep 13;12(1):96. doi: 10.1186/s40643-025-00936-y.
β-carotene, a carotenoid precursor to vitamin A, is widely employed in the food, pharmaceutical, and nutraceutical sectors. In this study, we present an economically sustainable strategy for β-carotene biosynthesis in Saccharomyces cerevisiae by engineering the yeast to utilize sucrose and agricultural by-products as alternative carbon and nitrogen sources. Specifically, the deletion of the GAL80 gene facilitated effective β-carotene synthesis directly from sucrose, circumventing the costly requirement for galactose induction. Using this engineered yeast strain, we achieved β-carotene titers of up to 23.30 ± 4.22 mg/L and content levels of 2.29 ± 0.16 mg/g dry cell weight (DCW). To further improve the economic viability and environmental sustainability, we evaluated the use of agricultural by-products-molasses as a carbon source and fish meal as a nitrogen source-in a fed-batch fermentation process, highlighting the potential of these substrates to replace refined feedstocks while achieving competitive β-carotene production levels. This approach yielded substantial β-carotene titers of 17.02 ± 0.40 mg/L and content levels of 2.90 ± 0.21 mg/g DCW. It also significantly reduced medium costs by up to 73% compared to conventional yeast extract and peptone-based media, demonstrating the practical potential of these low-cost, sustainable substrates for industrial applications. This study uniquely highlights the successful application of unrefined agricultural by-products, addressing key challenges in cost and sustainability. These findings represent an important advancement toward developing economically competitive and environmentally responsible microbial platforms for the production of β-carotene and other high-value biochemicals.
β-胡萝卜素是维生素A的类胡萝卜素前体，广泛应用于食品、制药和营养保健品行业。在本研究中，我们提出了一种经济可持续的策略，通过对酿酒酵母进行工程改造，使其利用蔗糖和农业副产品作为替代碳源和氮源，在酿酒酵母中进行β-胡萝卜素生物合成。具体而言，删除GAL80基因有助于直接从蔗糖中有效合成β-胡萝卜素，避免了对半乳糖诱导的高成本需求。使用这种工程酵母菌株，我们实现了高达23.30±4.22mg/L的β-胡萝卜素滴度和2.29±0.16mg/g干细胞重量（DCW）的含量水平。为了进一步提高经济可行性和环境可持续性，我们在分批补料发酵过程中评估了使用农业副产品糖蜜作为碳源和鱼粉作为氮源，突出了这些底物在替代精制原料同时实现具有竞争力的β-胡萝卜素生产水平的潜力。这种方法产生了17.02±0.40mg/L的大量β-胡萝卜素滴度和2.90±0.21mg/g DCW的含量水平。与传统的基于酵母提取物和蛋白胨的培养基相比，它还显著降低了培养基成本，最高可达73%，证明了这些低成本、可持续底物在工业应用中的实际潜力。本研究独特地突出了未精制农业副产品的成功应用，解决了成本和可持续性方面的关键挑战。这些发现代表了朝着开发具有经济竞争力和环境责任感的微生物平台以生产β-胡萝卜素和其他高价值生物化学品迈出的重要一步。
