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Record W4243231990 · doi:10.26434/chemrxiv.12899264.v1

Identification of a Tambjamine Gene Cluster in Streptomyces Reveals Convergent Evolution of the Biosynthetic Pathway

2020· preprint· en· W4243231990 on OpenAlexaff
Neil L. Grenade, Dragos S. Chiriac, Graeme W. Howe, Avena C. Ross

Bibliographic record

VenueChemRxiv · 2020
Typepreprint
Languageen
FieldMedicine
TopicMicrobial Natural Products and Biosynthesis
Canadian institutionsQueen's University
Fundersnot available
KeywordsStreptomyces albusGene clusterGeneBiologyComputational biologyBiosynthesisGenomeStreptomycesNatural productDNA sequencingGeneticsBiochemistryBacteria

Abstract

fetched live from OpenAlex

Bacterial natural products are an immensely valuable source of therapeutics. As modern DNA sequencing efforts provide increasing numbers of microbial genomes, it is clear that the molecules produced by most natural product biosynthetic gene clusters (BGCs) remain unknown. Genome mining makes use of bioinformatic techniques to elucidate the natural products produced by these “orphan” BGCs. Here, we report the use of sequence similarity networks (SSNs) and genome neighborhood networks (GNNs) to identify an orphan BGC that is responsible for the production of the antitumor tambjamine BE-18591 in Streptomyces albus NRRL B-2362. Although BE-18591 is a close structural analogue of tambjamine YP1 produced by Pseudoalteromonas tunicata, the biosynthetic routes to produce these molecules differ significantly. Notably, the C12-alkylamine tail that is appended onto the bipyrrole core of tambjamine YP1 is derived from fatty acids siphoned from the primary metabolism of the pseudoalteromonad, whilst the S. albus NRRL B-2362 BGC encodes a dedicated system for the de novo biosynthesis of the alkylamine portion of tambjamine BE-18591. These remarkably different biosynthetic strategies represent a striking example of convergent BGC evolution, with selective pressure for the production of tambjamines seemingly leading to the emergence of separate biosynthetic pathways in pseudoalteromonads and streptomycetes that ultimately produce closely related compounds

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation 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 score0.028
Threshold uncertainty score0.555

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
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)0.0000.000

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 head0.018
GPT teacher head0.242
Teacher spread0.224 · 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 teacher head, 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

Citations2
Published2020
Admission routes1
Has abstractyes

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