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Biochem Mol biol J

ISSN: 2471-8084

Volume 3, Issue 2

Metabolomics Conference 2017

August 29-30, 2017 Prague, Czech Republic



International Conference and Exhibition on

Metabolomics and Systems Biology


Page 25

Building and optimizing multi-enzyme

in vitro

cascade reactions

Nicholas Harmer

University of Exeter, UK


iocatalysis is becoming increasingly attractive for the

development of more efficient and cleaner chemical

synthetic processes. The combination of multiple enzyme

steps for cascade reactions allows for attractive one-pot

processes with reduced operating costs. While the use

of whole-cells have a number of advantages for these

reactions, the competing needs of the cell and limited

transport across the cell membrane can result in a low

final product concentration. In contrast, the use of isolated

enzymes allows reactions to be easily controlled, with the

use of stable enzymes such as those from thermophiles

offering economically competitive processes. For the

construction of novel enzymatic cascade reactions, there

is a need for well-defined modular enzyme building blocks

that canbequickly assembled for new reactions. Carboxylic

acid reductase (CARs) is a relatively undeveloped class

of enzyme which meets a demand in synthetic chemistry

for a green and regiospecific route to aldehydes from

their respective carboxylic acids. A thorough biochemical

characterization of four new CARs provides insight into

the operating parameters of these enzymes, while the

integration of a CAR into a seven enzyme

in vitro


reaction demonstrates their potential for green chemistry.

Mathematical modeling of the cascade allows for a detailed

understanding of the reaction and gives opportunity for

its optimization with respect to flux and cost. Our work

highlights the virtue of thorough enzyme characterization,

and of modeling reactions, to deliver new understanding

and build robust pathways.


Nicholas Harmer completed his PhD in the laboratory of Professor Sir Tom

Blundell in Cambridge, UK, researching the structure and interaction of

fibroblast growth factors, their receptors, and heparin. Following this, he took

a Post-doctoral position in Cambridge, investigating the structure and function

of a range of signaling proteins and bacterial enzymes. He then moved

to AstraZeneca R&D Mölndal, Sweden, where he worked as a Structural

Biologist in Drug Discovery. In 2007, he established his own laboratory at

University of Exeter, UK. His research work focusses on Synthetic Biology

and Drug Discovery applications for neglected diseases. His main interest is

in understanding enzymes more deeply, and in exploiting this understanding

to develop useful chemicals and biochemical. In 2017, he moved to Living

Systems Institute, Exeter.

[email protected]

Nicholas Harmer, Biochem Mol biol J, 3:2

DOI: 10.21767/2471-8084-C1-002