Strategies and perspectives of assembling multi-enzyme systems

Abstract

Multi-enzyme complexes have the potential to achieve high catalytic efficiency for sequence reactions due to their advantages in eliminating product inhibition, facilitating intermediate transfer and in situ regenerating cofactors. Constructing functional multi-enzyme systems to mimic natural multi-enzyme complexes is of great interest for multi-enzymatic biosynthesis and cell-free synthetic biotransformation, but with many challenges. Currently, various assembly strategies have been developed based on the interaction of biomacromolecules such as DNA, peptide and scaffolding protein. On the other hand, chemical-induced assembly is based on the affinity of enzymes with small molecules including inhibitors, cofactors and metal ions has the advantage of simplicity, site-to-site oriented structure control and economy. This review summarizes advances and progresses employing these strategies. Furthermore, challenges and perspectives in designing multi-enzyme systems are highlighted.

Keywords:

• Multi-enzyme systems
• enzyme assembly
• chemical induction
• structure-function analysis
• designed biosynthesis
• cascade reactions

Acknowledgements

This work was supported by the National Natural Science Foundation of China [No.41306124], the State Key Program of National Natural Science Foundation of China [No. 21336009], the Fundamental Research Funds for the Central Universities [No.2013121029], the Foundation of South Oceanographic Research Center of China in Xiamen [No.:14GYY011NF11], and the Public science and technology research funds projects of ocean [No.: 201505032–6].

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This work was supported by the State Key Program of National Natural Science Foundation of China (No. 21336009), the National Natural Science Foundation of China (No.41306124), the Fundamental Research Funds for the Central Universities (No.20720170033), the Foundation of South Oceanographic Research Center of China in Xiamen (No.:14GYY011NF11), and the Public science and technology research funds projects of ocean (No.: 201505032-6).