Evidence map›Paper›PMID 23776225›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2013

General approach to reversing ketol-acid reductoisomerase cofactor dependence from NADPH to NADH.

Sabine Brinkmann-Chen, Tilman Flock, Jackson K B Cahn, Christopher D Snow, Eric M Brustad, John A McIntosh, Peter Meinhold, Liang Zhang, Frances H Arnold

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
5.2field-weighted citation impact, top 3% of its field
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

46 citing papers in PubMed, 117 citations in OpenAlex.

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  17. Combinatorial library design for improving isobutanol production inFrontiers in bioengineering and biotechnology · 2022
    Article
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  20. Isobutanol Production by Autotrophic Acetogenic Bacteria.Frontiers in bioengineering and biotechnology · 2021
    Article
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

9 authors at 2 institutions in 2 countries.

Sabine Brinkmann-ChenCalifornia Institute of Technology, Pasadena, CA 91125, USA.
Tilman Flock
Jackson K B Cahn
Christopher D Snow
Eric M Brustad
John A McIntosh
Peter Meinhold
Liang Zhang
Frances H Arnold
California Institute of Technology · USGevo (United States) · US

Funding

Biocatalytic use of cytochrome P450 enzymesF32GM101792 · NIGMS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI MCINTOSH, JOHN ANDREW · 2012 to 2014
$150k
Evolution of cytochrome p450s for the diversification of drug scaffoldsF32GM087102 · NIGMS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI BRUSTAD, ERIC MICHAEL · 2009 to 2011
$118k
NIGMS NIH HHS F32 GM087102NIGMS NIH HHS F32GM087102NIGMS NIH HHS F32 GM101792NIGMS NIH HHS F32GM101792
6 · The paper itself

Abstract

To date, efforts to switch the cofactor specificity of oxidoreductases from nicotinamide adenine dinucleotide phosphate (NADPH) to nicotinamide adenine dinucleotide (NADH) have been made on a case-by-case basis with varying degrees of success. Here we present a straightforward recipe for altering the cofactor specificity of a class of NADPH-dependent oxidoreductases, the ketol-acid reductoisomerases (KARIs). Combining previous results for an engineered NADH-dependent variant of Escherichia coli KARI with available KARI crystal structures and a comprehensive KARI-sequence alignment, we identified key cofactor specificity determinants and used this information to construct five KARIs with reversed cofactor preference. Additional directed evolution generated two enzymes having NADH-dependent catalytic efficiencies that are greater than the wild-type enzymes with NADPH. High-resolution structures of a wild-type/variant pair reveal the molecular basis of the cofactor switch.

Indexed as

Amino Acid SequenceDirected Molecular EvolutionEscherichia coliEscherichia coli ProteinsKetol-Acid ReductoisomeraseModels, MolecularMolecular Sequence DataMutagenesis, Site-DirectedNADNADPProtein Structure, SecondarySequence Homology, Amino AcidEscherichia coli ProteinsKetol-Acid ReductoisomeraseNADNADPbranched-chain amino acid pathwaycofactor imbalance

Identifiers

PMID23776225
PMCPMC3704004
OpenAlexW2101532592

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.