Engineering a Seven Enzyme Biotransformation using Mathematical Modelling and Characterized Enzyme Parts (article)
dc.contributor.author | Finnigan, W | |
dc.contributor.author | Cutlan, R | |
dc.contributor.author | Snajdrova, R | |
dc.contributor.author | Adams, J | |
dc.contributor.author | Littlechild, J | |
dc.contributor.author | Harmer, NJ | |
dc.date.accessioned | 2019-07-23T08:39:22Z | |
dc.date.issued | 2019-06-05 | |
dc.description.abstract | Multi‐step enzyme reactions offer considerable cost and productivity benefits. Process models offer a route to understanding the complexity of these reactions, and allow for their optimization. Despite the increasing prevalence of multi‐step biotransformations, there are few examples of process models for enzyme reactions. From a toolbox of characterized enzyme parts, we demonstrate the construction of a process model for a seven enzyme, three step biotransformation using isolated enzymes. Enzymes for cofactor regeneration were employed to make this in vitro reaction economical. Good modelling practice was critical in evaluating the impact of approximations and experimental error. We show that the use and validation of process models was instrumental in realizing and removing process bottlenecks, identifying divergent behavior, and for the optimization of the entire reaction using a genetic algorithm. We validated the optimized reaction to demonstrate that complex multi‐step reactions with cofactor recycling involving at least seven enzymes can be reliably modelled and optimized. | en_GB |
dc.description.sponsorship | Biotechnology & Biological Sciences Research Council (BBSRC) | en_GB |
dc.description.sponsorship | GlaxoSmithKline | en_GB |
dc.identifier.citation | Published online 5 June 2019 | en_GB |
dc.identifier.doi | 10.1002/cctc.201900646 | |
dc.identifier.grantnumber | BB/K501001/1 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/38080 | |
dc.language.iso | en | en_GB |
dc.publisher | Wiley | en_GB |
dc.relation.url | https://doi.org/10.24378/exe.1623 | en_GB |
dc.rights | © 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. | en_GB |
dc.subject | Enzyme cascade | en_GB |
dc.subject | Kinetics | en_GB |
dc.subject | Pathway optimization | en_GB |
dc.subject | Isolated enzymes | en_GB |
dc.subject | Reaction engineering | en_GB |
dc.title | Engineering a Seven Enzyme Biotransformation using Mathematical Modelling and Characterized Enzyme Parts (article) | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2019-07-23T08:39:22Z | |
dc.identifier.issn | 1867-3880 | |
dc.description | This is the final version. Available on open access from Wiley via the DOI in this record | en_GB |
dc.description | The dataset associated with this article is located in ORE at: https://doi.org/10.24378/exe.1623 | en_GB |
dc.identifier.journal | ChemCatChem | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2019-05-31 | |
exeter.funder | ::Biotechnology & Biological Sciences Research Council (BBSRC) | en_GB |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2019-05-31 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2019-07-19T21:09:49Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2019-07-23T08:39:29Z | |
refterms.panel | A | en_GB |
Files in this item
This item appears in the following Collection(s)
Except where otherwise noted, this item's licence is described as © 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.