A roadmap for biocatalysis – functional and spatial orchestration of enzyme cascades

Abstract

SummaryAdvances in biological engineering and systems biology have provided new approaches and tools for the industrialization of biology. In the next decade, advanced biocatalytic systems will increasingly be used for the production of chemicals that cannot be made by current processes and/or where the use of enzyme catalysts is more resource efficient with a much reduced environmental impact. We expect that in the future, manufacture of chemicals and materials will utilize both biocatalytic and chemical synthesis synergistically. The realization of such advanced biomanufacturing processes currently faces a number of major challenges. Ready‐to‐deploy portfolios of biocatalysts for design to production must be created from biological diverse sources and through protein engineering. Robust and efficient multi‐step enzymatic reaction cascades must be developed that can operate simultaneously in one‐pot. For this to happen, bio‐orthogonal strategies for spatial and temporal control of biocatalyst activities must be developed. Promising approaches and technologies are emerging that will eventually lead to the design of in vitro biocatalytic systems that mimic the metabolic pathways and networks of cellular systems which will be discussed in this roadmap.

Co‐immobilized Phosphorylated Cofactors and Enzymes as Self‐Sufficient Heterogeneous Biocatalysts for Chemical Processes

“…Industrial biocatalysis is transforming chemical manufacturing towards more sustainable and environmentally friendly processes 1. Some of the most interesting reactions in industrial biocatalysis are catalyzed by cofactor‐dependent enzymes such as NADH‐dependent reductases and oxidases, PLP‐dependent transaminases, and FAD + ‐dependent oxygenases 2.…”

Three‐Enzyme Phosphorylase Cascade Immobilized on Solid Support for Biocatalytic Synthesis of Cello−oligosaccharides

“…The issue encountered with Z− Cu CbP does not, therefore, detract from the conceptual appeal and the potential general utility of the approach. The principle of Z basic2 ‐directed multienzyme co‐immobilization on anionic supports appears to be broadly applicable to biocatalytic cascade reactions . More specifically in the oligosaccharide and specialty carbohydrate synthesis, its use might be extended to various cascades of glycoside phosphorylases or glycosyltransferases that have shown promising performances when used as soluble enzymes.…”

Magnetic Microreactors with Immobilized Enzymes—From Assemblage to Contemporary Applications

“…An in vitro system can be made with the ability to assemble non-natural biocatalytic cascade reactions by mixing and matching enzymes from different sources to generate a desirable end product. Systems biocatalysis has evolved as a novel territory with the aim to design artificial metabolic networks for in vitro biocatalysis [35,36]. Microfluidic systems are already used in this field, as they enable miniaturization and compartmentalization, with small biocatalyst volumes and high spatiotemporal reaction control [15].…”