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Record W4319965089 · doi:10.1099/acmi.0.000572.v1.3

Reviewer response for version 1

2023· peer-review· en· W4319965089 on OpenAlexaff
Rebecca E. McHugh, Josephine Giard, Robyn E Braes, Iain J. W. McKean, Andrew J. Roe, Paul A. Hoskisson

Bibliographic record

Venuenot available
Typepeer-review
Languageen
FieldMedicine
TopicMicrobial Natural Products and Biosynthesis
Canadian institutionsInstitute of Infection and Immunity
Fundersnot available
KeywordsVirulenceEscherichia coliMicrobiologyBiologyFermentationHeterologousSecondary metaboliteSecretionYeast extractMode of actionBioassayGene clusterStreptomyces coelicolorGeneBiochemistryMutantGenetics

Abstract

fetched live from OpenAlex

Aurodox is a specialised metabolite of Streptomyces goldiniensis originally identified for its anti-streptococcal and anti-staphylococcal activity. More recently, there has been a renewed focus on the study of aurodox as the compound has been shown to inhibit virulence in both Enteropathogenic and Enterohemorrhagic Escherichia coli (EPEC/EHEC). Aurodox is able to inhibit host colonization in EPEC and EHEC infections via the downregulation of the Type III Secretion System – a major virulence factor in these pathogens. To further investigate activity, increased quantities of the compound are required for in-depth mechanism of action studies. To identify suitable aurodox production conditions, a number of relevant fermentation media were tested for enhanced aurodox yield, followed by bioassay and Liquid Chromatography Mass Spectrometry analysis. Glucose Yeast Extract medium (GYM) was identified as the leading production medium tested. Further analysis of S. goldiniensis growth in GYM medium established the optimum temporal range for aurodox production. A minimum growth period of 154 hours is required for detectable aurodox production in S. goldiniensis fermentations in liquid GYM medium. To improve overall aurodox titres, a heterologous expression (HE) approach was taken and four potential HE hosts were investigated. These data indicated that the aurodox biosynthetic gene cluster can be heterologously expressed in both S. collinus Tü365 and S. coelicolor M1152, with increased aurodox titres compared to those of S. goldiniensis. This work demonstrates how traditional physiological analysis and modern genetic techniques can be combined to improve natural product production for detailed mode-of-action studies.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.018
metaresearch head score (Gemma)0.204
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesInsufficient payload (model declined to judge)
Consensus categoriesInsufficient payload (model declined to judge)
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: Not applicable
GenreCandidate signal: Other · Consensus signal: none
Teacher disagreement score0.358
Threshold uncertainty score0.510

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0180.204
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0030.003
Bibliometrics0.0050.003
Science and technology studies0.0030.002
Scholarly communication0.0100.007
Open science0.0050.006
Research integrity0.0080.009
Insufficient payload (model declined to judge)0.6420.315

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.054
GPT teacher head0.343
Teacher spread0.289 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; the direct Gemma label and the distilled Codex classifier agree on what is shown here.

Study designNot applicable
Domainnot available
GenreOther

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2023
Admission routes1
Has abstractyes

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