Evidence map›Paper›PMID 31598184›Full record

ArticleChemCatChem2019

Engineering a Seven Enzyme Biotransformation using Mathematical Modelling and Characterized Enzyme Parts.

William Finnigan, Rhys Cutlan, Radka Snajdrova, Joseph P Adams, Jennifer A Littlechild, Nicholas J Harmer

Abstract read
In one paragraph

Article in ChemCatChem, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

William FinniganDepartment of Biosciences University of Exeter Henry Wellcome Building for Biocatalysis Stocker Road Exeter EX4 4QD UK.
Rhys CutlanLiving Systems Institute University of Exeter Stocker Road Exeter EX4 4QDm UK.
Radka SnajdrovaGlaxoSmithKline R&D Ltd Medicines Research Centre Gunnels Wood Road, Stevenage Hertfordshire SG1 2NY UK.
Joseph P AdamsGlaxoSmithKline R&D Ltd Medicines Research Centre Gunnels Wood Road, Stevenage Hertfordshire SG1 2NY UK.
Jennifer A LittlechildDepartment of Biosciences University of Exeter Henry Wellcome Building for Biocatalysis Stocker Road Exeter EX4 4QD UK.
Nicholas J HarmerDepartment of Biosciences University of Exeter Henry Wellcome Building for Biocatalysis Stocker Road Exeter EX4 4QD UK.ORCID 0000-0002-4073-0505

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Enzyme cascadeIsolated enzymesKineticsPathway optimizationReaction engineering

Identifiers

PMID31598184
PMCPMC6774274

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.