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Identification of Genes Essential for Sulfamate and Fluorine Incorporation During Nucleocidin Biosynthesis

2022· article· en· W4225395075 on OpenAlexaff
Ola Pasternak, David L. Zechel

Bibliographic record

VenueThe FASEB Journal · 2022
Typearticle
Languageen
FieldMedicine
TopicPneumocystis jirovecii pneumonia detection and treatment
Canadian institutionsQueen's University
Fundersnot available
KeywordsStreptomycesBiosynthesisNatural productSecondary metaboliteChemistryStereochemistryGene clusterStreptomyces hygroscopicusNucleosideBiochemistryGeneBiologyBacteriaGenetics

Abstract

fetched live from OpenAlex

Nucleocidin, a secondary metabolite of Streptomyces calvus (1), is a derivative of adenosine that contains 4’‐fluorine and 5’‐ O ‐sulfamate groups. Both substituents are rarely observed in natural products. A minimal biosynthetic gene cluster has yet to be defined for nucleocidin, and at least 24 genes appear to be involved. To date, only two functions have been assigned, neither of which are directly involved in sulfamate biosynthesis or fluorination (2, 3). In this presentation, we present biosynthetic studies on two newly discovered producers of nucleocidin, Streptomyces virens B‐24331 and Streptomyces aureorectus B‐24301 (4). Both strains are shown to be significantly (up to 30‐fold) better producers of nucleocidin than S. calvus . Gene disruption experiments in S. virens have identified, for the first time, genes differentially impacting sulfmate and 4’‐fluorine biosynthesis. These and additional results will be presented. References : (1) Zhu, X. M., et al., Biosynthesis of the Fluorinated Natural Product Nucleocidin in Streptomyces calvus Is Dependent on the bldA ‐Specified Leu‐tRNA(UUA) Molecule. ChemBioChem 2015 , 16 , 2498–2506. (2) Feng, X., et al . Two 3’‐ O ‐b‐glucosylated nucleoside fluorometabolites related to nucleocidin in Streptomyces calvus. Chem. Sci . 2019 , 10 , 9501‐9505. (3) Ngivprom, U., et al . Characterization of NucPNP and NucV involved in theearly steps of nucleocidin biosynthesis in Streptomyces calvus . RSC Adv., 2021 , 11 , 3510‐3515. (4) Chen, Y., et al., Streptomyces aureorectus DSM 41692 and Streptomyces virens DSM 41465 are producers of the antibiotic nucleocidin and 4’‐fluoroadenosine is identified as a co‐product. Org. Biomol. Chem . 2021 , DOI: 10.1039/d1ob01898a.

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)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.012
GPT teacher head0.243
Teacher spread0.231 · 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; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

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Citations0
Published2022
Admission routes1
Has abstractyes

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