Yan Dong, Cai Xue, Xue Hailong, Zhen Ni, Wu Yushuang, Liu Zhiqiang, Li Mian, Zheng Yuguo
Zhejiang Huakang Pharmaceutical Co., Ltd., Kaihua 324302, Zhejiang, China.
College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, Zhejiang, China.
Sheng Wu Gong Cheng Xue Bao. 2024 Aug 25;40(8):2626-2643. doi: 10.13345/j.cjb.240220.
D-mannitol is a six-carbon sugar alcohol and one of the most abundant polyols in the nature. With antioxidant and osmotic pressure-regulating effects and non-metabolism by the human body, D-mannitol has been widely used in functional food and pharmaceutical industries. At present, a major way for industrial production of D-mannitol is chemical hydrogenation. In addition, D-Mannitol can be produced by microbial metabolism or catalysis. Compared with the chemical hydrogenation, the microbial methods for synthesizing mannitol do not produce sorbitol as a by-product and have the advantages of mild reaction conditions, strong specificity, and high conversion rate. Microbial fermentation is praised for easy access of strains and raw materials and simple separation of the product. Microbial catalysis usually adopts a multi-enzyme coupling strategy, which uses enzymes produced by engineered bacteria for whole-cell catalysis, and the cofactor recycling pathway is introduced to replenish expensive cofactor. This method can achieve high yields with cheap substrates under mild conditions without the formation of by-products. However, the application of microbial methods in the industrial production of D-mannitol is limited by the high costs of fermentation media and substrates and the long reaction time. This article reviews the reported microbial methods for producing D-mannitol, including the use of high-yielding strains and their fermentation processes, the utilization of low-cost substrates, whole-cell catalytic strategies, and the process control for high productivity. The biosynthesis of mannitol is not only of great significance for promoting industrial upgrading and realizing green manufacturing, but also provides strong support for the development of new bio-based products to meet the growing market demand. With the continuous improvement of technological innovation and industrial chain, it is expected to become one of the main ways of mannitol production in the future.
D-甘露醇是一种六碳糖醇,是自然界中含量最丰富的多元醇之一。D-甘露醇具有抗氧化和调节渗透压的作用,且人体不代谢,已广泛应用于功能食品和制药行业。目前,D-甘露醇的工业生产主要方法是化学氢化法。此外,D-甘露醇还可通过微生物代谢或催化生产。与化学氢化法相比,微生物合成甘露醇的方法不会产生山梨醇副产物,具有反应条件温和、特异性强、转化率高的优点。微生物发酵因菌株和原料易于获取、产物分离简单而备受赞誉。微生物催化通常采用多酶偶联策略,利用工程菌产生的酶进行全细胞催化,并引入辅因子循环途径以补充昂贵的辅因子。该方法在温和条件下使用廉价底物即可实现高产率,且不形成副产物。然而,微生物方法在D-甘露醇工业生产中的应用受到发酵培养基和底物成本高以及反应时间长的限制。本文综述了已报道的微生物生产D-甘露醇的方法,包括高产菌株的使用及其发酵过程、低成本底物的利用、全细胞催化策略以及高生产率的过程控制。甘露醇的生物合成不仅对推动产业升级和实现绿色制造具有重要意义,也为开发新型生物基产品以满足不断增长的市场需求提供了有力支持。随着技术创新和产业链的不断完善,有望成为未来甘露醇生产的主要方式之一。