Enzyme catalysed reactions for high-value applications
Professor Nicholas Turner, University of Manchester, UK
This lecture will describe recent work from our laboratory aimed at developing new biocatalysts for enantioselective organic synthesis, with emphasis on the design of in vitro and in vivo cascade processes for generating chiral pharmaceutical building blocks. By applying the principles of ‘biocatalytic retrosynthesis’ we have shown that it is increasingly possible to design new synthetic routes to target molecules in which biocatalysts are used in the key bond forming steps.
The integration of several biocatalytic transformations into multi-enzyme cascade systems, both in vitro and in vivo, will be addressed in the lecture. In this context monoamine oxidase (MAO-N) has been used in combination with other biocatalysts and chemocatalysts in order to complete a cascade of enzymatic reactions. Other engineered biocatalysts that can be used in the context of cascade reactions include w-transaminases, ammonia lyases, amine dehydrogenases, imine reductases, and artificial transfer hydrogenases. We shall also present recent work regarding the discovery of a new biocatalyst for enantioselective reductive amination and show how these enzymes can be used to carry out redox neutral amination of alcohols via ‘hydrogen borrowing’.
Biocatalytic recycling of plastic
Professor Wolfgang Zimmermann, Leipzig University, Germany
The global production of plastics made from non-renewable fossil feedstocks has grown more than 20-fold since 1964. While more than eight billion metric tons of plastics have been produced until today, only a small fraction is currently collected for recycling and large amounts of plastic waste are ending up in landfills or in the oceans. Pollution caused by accumulating plastic waste in the environment has therefore become world-wide a very serious problem.
Synthetic polyesters such as polyethylene terephthalate (PET) have widespread use in packaging materials, beverage bottles, foams, coatings, and fibers. Recently it has been shown that amorphous PET materials can be completely hydrolyzed by microbial enzymes at mild reaction conditions in aqueous media. Due to the restricted mobility of the polymer chains at ambient temperatures, an efficient biocatalytic degradation has to be performed close to the glass transition temperature of PET of about 70°C. Thermostable enzymes like those produced by actinomycete bacteria have therefore emerged as the most promising catalysts for the hydrolysis of PET to its monomeric building blocks. In a circular economy, the resulting monomers can be recovered and reused to manufacture novel PET again or other products without depleting fossil feedstocks. The enzymatic degradation of post-consumer plastic waste thereby represents an innovative, environmentally benign, and sustainable alternative to conventional chemical recycling processes. By the construction of powerful biocatalysts employing protein engineering techniques and an optimization of the bioprocess parameters, a biocatalytic recycling of PET can be further developed towards industrial applications.
Biocatalysis and biomass conversion: enabling a circular economy
Professor Roger Sheldon, Delft University of Technology
Two of the grand societal and technological challenges of the twenty first century are the 'greening' of chemicals manufacture and the ongoing transition to a bio-based economy: that is a sustainable, carbon-neutral economy based on renewable biomass as the raw material. These challenges are motivated by the need to eliminate environmental degradation and mitigate climate change. Waste minimisation and waste valorisation in a circular economy constitute a point of overlap of these grand challenges. In a bio-based economy, ideally waste biomass, particularly agricultural and forestry residues and food supply chain waste, are converted to liquid fuels, commodity chemicals, and biopolymers by employing clean, catalytic processes.
Biocatalysis has the right credentials to achieve this goal. Enzymes are biocompatible (sometimes even edible), biodegradable and essentially non-hazardous. Additionally, they are derived from inexpensive renewable resources which are readily available and not subject to the large price fluctuations which undermine the long term commercial viability of catalysts derived from scarce precious metals. Moreover, thanks to spectacular advances in molecular biology the landscape of biocatalysis has dramatically changed in the last two decades. Developments in (meta)genomics in combination with 'big data' analysis have revolutionised new enzyme discovery and developments in protein engineering by directed evolution have enabled dramatic improvements in their performance. These developments have their confluence in the bio-based circular economy.
Cleaner NADH recycling for biocatalytic chemical synthesis
Professor Kylie Vincent, University of Oxford, UK
Enzymes are powerful catalysts for selective oxidation and reduction reactions, but one of the barriers to the scale-up of biocatalysis for bulk chemical transformations is the reliance of many of these enzymes on expensive nicotinamide cofactors, NADH or NADPH. The cost and complexity of these cofactors mean that they must be continuously recycled during chemical transformations. Recycling of the reduced cofactors is typically achieved using glucose as a sacrificial oxidant (hydride donor), generating substantial carbon-based waste. This talk will explore alternative, cleaner possibilities for recycling the reduced cofactors for reductive chemical synthesis, using hydrogen gas or electrochemical processes as the reductant for NADH or NADPH. Further, we show that immobilisation of the cofactor recycling system, together with the enzyme of interest, on a solid support offers advantages for scale-up and re-use of biocatalysts in batch reactors, and possibilities for implementing biocatalysis in continuous flow reactors. Developments in these areas will be critical in enabling biocatalysis to move beyond the small-volume, fine chemicals sector so that enzymes can play a significant role in circular transformations of commodity chemicals in a sustainable future economy