辅酶自循环的氧化还原级联体系在生物催化过程中的应用:机遇与挑战

Application of the redox cascade systems with coenzyme self-cycling in biocatalytic processes: opportunities and challenges

氧化还原酶是生物催化过程中应用最为广泛的一类酶,其可以在温和条件下高选择性进行催化,在化工、医药、农业等领域发挥着重要作用。大部分氧化还原酶催化的反应需要烟酰胺辅因子参与。烟酰胺辅因子价格昂贵,大量外源添加会加重成本,无法满足工业生产的要求,因此开发高效经济的辅因子再生策略对氧化还原酶的工业应用具有重要意义。在常用的辅因子再生方法中,酶法因其高效绿色的特点得到了广泛的应用。其中,辅酶自循环的氧化还原级联体系是一种特殊的酶法再生烟酰胺辅因子策略,它能结合多酶级联催化,在不添加任何共底物的情况下,完成烟酰胺辅因子内部的自给自足循环再生。相比其他酶法再生策略,其具有副产物少、原子经济性高等突出优势。本文按照酶促反应进行的顺序将辅酶自循环的氧化还原级联体系分为四大类进行讨论,并以醇/醛脱氢酶为基础,综述了该体系应用于生物催化过程的机遇与挑战,为进一步开发更高效的辅酶自循环的氧化还原级联体系提供思路。

Oxidoreductases are one of the most widely used enzymes in biocatalysis process.It can catalyze under mild conditions with high selectivity and play an important role in chemical,pharmaceutical,agriculture and so on.Most oxidoreductase-catalyzed reactions require the nicotinamide cofactor.Due to the high cost of nicotinamide cofactor,large amount of usage is not practical for industrial applications.Thus,it is of great significance to develop efficient and economical cofactor regeneration strategies for the industrial application of oxidoreductases.Among the commonly used cofactor regeneration methods,enzymatic method is frequently used based on its high efficiency and environmental friendliness.Redox-neutral system is a special strategy for enzymatic regeneration of nicotinamide cofactors.It can be combined with multi-enzyme cascade catalysis to self-sufficiently complete the regeneration of nicotinamide cofactors without adding any co-substrates.It has the advantages of few by-products and high atomic economy compared with conventional enzymatic regeneration methods.In this review,the redoxneutral system is divided into four categories to discuss according to the sequence of multi-enzymatic cascade reactions.Based on alcohol/aldehyde dehydrogenase,the opportunities and challenges of the redox-neutral system in biocatalysis process are reviewed,which can provide positive ideas for designing a more efficient redox-neutral systems in the further.