Evidence map›Paper›PMID 21644826›Full record

ArticleFuture medicinal chemistry2011

Assessing directed evolution methods for the generation of biosynthetic enzymes with potential in drug biosynthesis.

David P Nannemann, William R Birmingham, Robert A Scism, Brian O Bachmann

Abstract read
In one paragraph

Article in Future medicinal chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing 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

18 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. MonokaryoticInternational journal of molecular sciences · 2021
    Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Review
  13. Article
  14. Rosetta and the Design of Ligand Binding Sites.Methods in molecular biology (Clifton, N.J.) · 2016
    Article
  15. Review
  16. Article
  17. Review
  18. 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

4 authors.

David P NannemannChemistry Department, 7330 Stevenson Center, Vanderbilt University, Nashville, TN 37235, USA.
William R Birmingham
Robert A Scism
Brian O Bachmann

Funding

Chemistry-Biology Interface Training GrantT32GM065086 · NIGMS · VANDERBILT UNIVERSITY · PI BACHMANN, BRIAN O, SULIKOWSKI, GARY ALLEN · 2002 to 2022
$7.0M
Biosynthesis of Hypotensive Phosphonopeptide Natural ProductsR01GM077189 · NIGMS · VANDERBILT UNIVERSITY · PI BACHMANN, BRIAN O · 2006 to 2010
$1.1M
NIGMS NIH HHS GM077189NIGMS NIH HHS R01 GM077189NIGMS NIH HHS T32 GM065086
6 · The paper itself

Abstract

To address the synthesis of increasingly structurally diverse small-molecule drugs, methods for the generation of efficient and selective biological catalysts are becoming increasingly important. 'Directed evolution' is an umbrella term referring to a variety of methods for improving or altering the function of enzymes using a nature-inspired twofold strategy of mutagenesis followed by selection. This article provides an objective assessment of the effectiveness of directed evolution campaigns in generating enzymes with improved catalytic parameters for new substrates from the last decade, excluding studies that aimed to select for only improved physical properties and those that lack kinetic characterization. An analysis of the trends of methodologies and their success rates from 81 qualifying examples in the literature reveals the average fold improvement for k (cat) (or V (max)), K (m) and k (cat)/K (m) to be 366-, 12- and 2548-fold, respectively, whereas the median fold improvements are 5.4, 3 and 15.6. Further analysis by enzyme class, library-generation methodology and screening methodology explores relationships between successful campaigns and the methodologies employed.

Indexed as

Directed Molecular EvolutionBiocatalysisEnzymesKineticsMeta-Analysis as TopicMutagenesisPharmaceutical PreparationsProtein EngineeringEnzymesPharmaceutical Preparations

Identifiers

PMID21644826
PMCPMC3155183

What OpenQuestion holds

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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.