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Record W4384943875 · doi:10.1021/jacs.3c04447

Reductases Produce Nitric Oxide in an Alternative Pathway to Form the Diazeniumdiolate Group of <scp>l</scp>-Alanosine

2023· article· en· W4384943875 on OpenAlexafffund
Menghua Wang, Katherine S. Ryan

Bibliographic record

VenueJournal of the American Chemical Society · 2023
Typearticle
Languageen
FieldPharmacology, Toxicology and Pharmaceutics
TopicChemical Reactions and Isotopes
Canadian institutionsUniversity of British Columbia
FundersNatural Sciences and Engineering Research Council of CanadaMichael Smith Health Research BC
KeywordsChemistryNitric oxideGroup (periodic table)StereochemistryMedicinal chemistryCombinatorial chemistryOrganic chemistry

Abstract

fetched live from OpenAlex

l -Alanosine is a diazeniumdiolate ( N -nitrosohydroxylamine) antibiotic that inhibits MTAP-deficient tumor cells by blocking de novo adenine biosynthesis. Previous work revealed the early steps in the biosynthesis of l -alanosine. In the present study, we used genome mining to discover two new l -alanosine-producing strains that lack the a spartate- n itro s uccinate pathway genes found in the original l -alanosine producer. Instead, nitrate is reduced with a unique set of nitrate–nitrite reductases. These enzymes are typically used as part of the nitrogen cycle for denitrification or assimilation, and our report here shows how enzymes from the nitrogen cycle can be repurposed for the biosynthesis of specialized metabolites. The widespread distribution of nitric-oxide-producing reductases also indicates a potential for the discovery of new nitric-oxide-derived natural products.

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 score0.001
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)0.0000.001

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 head0.059
GPT teacher head0.385
Teacher spread0.325 · 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".

Quick stats

Citations23
Published2023
Admission routes2
Has abstractyes

Explore more

Same venueJournal of the American Chemical SocietySame topicChemical Reactions and IsotopesFrench-language works237,207