生物法制备甘露醇研究进展  

Recent advances in the bioproduction of mannitol

作　　者：阎冬 蔡雪 薛海龙 甄妮 吴玉双 柳志强 李勉 郑裕国 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)

机构地区：[1]浙江华康药业股份有限公司,浙江开化324302 [2]浙江工业大学生物工程学院,浙江杭州310014

出　　处：《生物工程学报》2024年第8期2626-2643,共18页Chinese Journal of Biotechnology

基　　金：国家重点研发计划(2022YFC2105400);浙江省“尖兵”“领雁”研发攻关计划(浙科发规(2023C01113))。

摘　　要：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,具有抗氧化保护、调节渗透压和不可代谢等特性,已广泛应用于功能性食品和制药行业中。目前工业化生产D-甘露醇的主要方法为化学加氢法。D-甘露醇也可由微生物代谢或者微生物催化生成,相比化学加氢法,生物法合成甘露醇不产生副产物山梨醇,且具有条件温和、专一性强、转化率高的优点。其中微生物发酵法的微生物菌种和发酵原料来源广泛易得,产物易于分离。微生物催化法采用多酶偶联的反应策略,利用工程菌产酶进行全细胞催化,同时引入辅因子循环途径使得昂贵的辅因子得到补充,可以在温和的条件下利用廉价底物获得较高的产率且没有副产物生成。然而,限制利用微生物法进行工业化生产D-甘露醇的一个主要因素是成本昂贵,包括发酵培养基和底物成本高、耗费时间长等。本文综述了微生物法生产D-甘露醇的方法,包括使用的高产发酵菌株及其发酵工艺、低成本底物的利用、全细胞催化法工程菌株开发策略以及高生产率的工艺调控等。生物法合成甘露醇不仅对促进产业升级、实现绿色制造具有重要意义,同时也为开发新型生物基产品、满足日益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,未来其有望成为甘露醇生产的主要方式之一。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.

关 键 词：甘露醇生产 微生物发酵 全细胞催化 合成生物学 辅因子循环 

分 类 号：TQ923[轻工技术与工程—发酵工程]