Evidence map›Paper›PMID 32875119›Full record

ArticleScience advances2020

Reengineering biocatalysts: Computational redesign of chondroitinase ABC improves efficacy and stability.

Marian H Hettiaratchi, Matthew J O'Meara, Teresa R O'Meara, Andrew J Pickering, Nitzan Letko-Khait, Molly S Shoichet

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

23 citing papers in PubMed, 51 citations in OpenAlex.

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  12. One-shot design elevates functional expression levels of a voltage-gated potassium channel.Protein science : a publication of the Protein Society · 2024
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  16. Decoding CRISPR-Cas PAM recognition with UniDesign.Briefings in bioinformatics · 2023
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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 at 3 institutions in 2 countries.

Marian H HettiaratchiDepartment of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON M5S 3E5, Canada.ORCID 0000-0001-8187-4575
Matthew J O'MearaDepartment of Computational Medicine and Bioinformatics, University of Michigan, 100 Washtenaw Ave. #2017, Ann Arbor, MI 48109, USA.ORCID 0000-0002-3128-5331
Teresa R O'MearaDepartment of Microbiology and Immunology, University of Michigan, 1150 W. Medical Center Dr., Ann Arbor, MI 48109 USA.ORCID 0000-0002-8901-0154
Andrew J PickeringDepartment of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON M5S 3E5, Canada.ORCID 0000-0002-1496-7752
Nitzan Letko-KhaitDepartment of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON M5S 3E5, Canada.
Molly S ShoichetDepartment of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON M5S 3E5, Canada.ORCID 0000-0003-1830-3475
University of Toronto · CAUniversity of Michigan · USWashtenaw Community College · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Maintaining biocatalyst stability and activity is a critical challenge. Chondroitinase ABC (ChABC) has shown promise in central nervous system (CNS) regeneration, yet its therapeutic utility is severely limited by instability. We computationally reengineered ChABC by introducing 37, 55, and 92 amino acid changes using consensus design and forcefield-based optimization. All mutants were more stable than wild-type ChABC with increased aggregation temperatures between 4° and 8°C. Only ChABC with 37 mutations (ChABC-37) was more active and had a 6.5 times greater half-life than wild-type ChABC, increasing to 106 hours (4.4 days) from only 16.8 hours. ChABC-37, expressed as a fusion protein with Src homology 3 (ChABC-37-SH3), was active for 7 days when released from a hydrogel modified with SH3-binding peptides. This study demonstrates the broad opportunity to improve biocatalysts through computational engineering and sets the stage for future testing of this substantially improved protein in the treatment of debilitating CNS injuries.

Identifiers

PMID32875119
PMCPMC7438101
OpenAlexW3061328166

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.