tooluniverse-natural-product-dereplication

name tooluniverse-natural-product-dereplication description Dereplicate a putative natural product and assign its chemical taxonomy. Use to answer "is [compound] a known natural product", "what microbe/organism produces [compound]", "what chemical class is [compound]", "dereplicate this metabolite (by formula/exact mass/InChIKey/SMILES)", or "classify this molecule into ChemOnt". Searches NPAtlas for known microbial natural products (producing organism + literature reference), assigns the ChemOnt kingdom→superclass→class→subclass hierarchy via ClassyFire, resolves systematic IUPAC names to structure via OPSIN, and cross-references identity in PubChem. NOT for general drug/compound identity or ADMET (use tooluniverse-chemical-compound-retrieval / tooluniverse-small-molecule-discovery) and NOT for metabolomics pathway/enrichment analysis (use tooluniverse-metabolomics skills). disable-model-invocation true Natural Product Dereplication & Chemotaxonomy Decide whether a putative natural product is already known , identify the microbe that produces it , attach the literature reference , and assign its ChemOnt chemical class . This is the dereplication question every NP chemist and metabolomics analyst asks of a new feature: "have we seen this before, and what makes it?" LOOK UP DON'T GUESS : Never assume an NPAID, producing organism, exact mass, or chemical class. Every identity, provenance, and taxonomy claim must come from a live tool call. Scope (microbial NPs only) : NPAtlas covers natural products from bacteria and fungi . It does NOT cover plant, animal, or marine-invertebrate metabolites unless a microbial producer was reported. A "no NPAtlas hit" therefore means not a known microbial NP — it does not prove the molecule is novel in an absolute sense. Backing Tools (all keyless; verify before quoting) Tool Input Returns NPAtlas_search_compounds name / inchikey / formula / smiles , limit list of {npaid, name, molecular_formula, molecular_weight, exact_mass, inchikey, smiles}. (origin_organism is null here — fetch the full record for provenance) NPAtlas_get_compound npaid (e.g. NPA014588 ) full record incl. origin_organism (producing microbe + taxonomic lineage) and origin_reference (title/doi/journal/year) ClassyFire_classify_by_inchikey inchikey (full 27-char) ChemOnt kingdom→superclass→class→subclass→direct_parent, molecular_framework, substituents. classified:false if not in cache OPSIN_name_to_structure name (systematic IUPAC) smiles / inchi / inchikey. parsed:false for trade/trivial names PubChem_get_CID_by_compound_name name {IdentifierList:{CID:[...]}} PubChem_get_compound_properties_by_CID cid , properties (e.g. ["MolecularFormula","MolecularWeight","InChIKey","IUPACName"] ) property table — use to obtain an InChIKey for arbitrary compounds Workflow Phase 0: Classify input — name / formula / exact mass / InChIKey / SMILES? Phase 1: Obtain an InChIKey (the universal key for ClassyFire & precise NPAtlas match) Phase 2: Dereplicate against NPAtlas (known microbial NP? which organism? which paper?) Phase 3: Assign ChemOnt chemical class via ClassyFire Phase 4: Cross-reference identity in PubChem Phase 5: Report — known/novel call + provenance + class hierarchy + interpretation note Phase 0 — Classify the input Full InChIKey (27 chars, XXXXXXXXXXXXXX-XXXXXXXXXX-X ) → skip to Phase 2; it is already the universal key. Molecular formula / exact mass → go straight to NPAtlas formula search (Phase 2); these are the rawest dereplication inputs (typical of an untargeted MS feature). SMILES → usable directly in NPAtlas_search_compounds(smiles=...) ; also feed to PubChem for an InChIKey. Systematic IUPAC name (e.g. 2-acetyloxybenzoic acid ) → Phase 1 via OPSIN. Trivial / trade / common name (e.g. staurosporine , penicillin ) → Phase 1 via PubChem (OPSIN will return parsed:false for these). Phase 1 — Obtain an InChIKey # Systematic IUPAC name → structure (OPSIN). parsed:false ⇒ fall through to PubChem. op = tu.tools.OPSIN_name_to_structure(name= "2-acetyloxybenzoic acid" ) inchikey = op[ "data" ][ "inchikey" ] # only if op["data"]["parsed"] # Trivial/common name → PubChem CID → properties (incl. InChIKey) cid = tu.tools.PubChem_get_CID_by_compound_name(name= "staurosporine" )[ "data" ][ "IdentifierList" ][ "CID" ][ 0 ] props = tu.tools.PubChem_get_compound_properties_by_CID( cid=cid, properties=[ "MolecularFormula" , "MolecularWeight" , "InChIKey" , "IUPACName" ]) inchikey = props[ "data" ][ "PropertyTable" ][ "Properties" ][ 0 ][ "InChIKey" ] The InChIKey is what makes dereplication exact: an InChIKey match is a structure match; a name match is not (synonyms, analogs, and salts share names). Phase 2 — Dereplicate against NPAtlas Search by the most specific key available. Prefer InChIKey (exact structure), then formula (catches isomers — useful for an MS feature with only a formula), then name (loosest — returns analogs). # Exact, structure-level hits = tu.tools.NPAtlas_search_compounds(inchikey= "HKSZLNNOFSGOKW-FYTWVXJKSA-N" , limit= 5 ) # MS-feature style (formula or exact mass) — expect multiple isomeric hits hits = tu.tools.NPAtlas_search_compounds(formula= "C28H26N4O3" , limit= 10 ) For each candidate NPAID, fetch the full record to get the producing organism and reference (search results carry origin_organism: null ): rec = tu.tools.NPAtlas_get_compound(npaid= "NPA014588" )[ "data" ] organism = rec[ "origin_organism" ][ "name" ] # e.g. "Streptomyces" lineage = rec[ "origin_organism" ][ "ancestors" ] # domain→...→family reference = rec[ "origin_reference" ] # title, doi, journal, year Phase 3 — Assign ChemOnt chemical class cf = tu.tools.ClassyFire_classify_by_inchikey(inchikey=inchikey)[ "data" ] # cf["kingdom"], cf["superclass"], cf["class"], cf["subclass"], cf["direct_parent"] # cf["molecular_framework"], cf["substituents"] If classified:false , the InChIKey is not in the ClassyFire cache — report the class as unavailable (do not invent one). A correct InChIKey is required; a wrong stereo/protonation layer will miss the cache. Phase 4 — Cross-reference identity in PubChem Confirm the same molecule exists in PubChem (CID, IUPAC name, formula, MW) so the identity is anchored to a second independent database. Disagreement in molecular formula between NPAtlas and PubChem is a red flag that the name/structure resolution went astray. Phase 5 — Report Deliver: Dereplication call — Known microbial NP (with NPAID) or No NPAtlas match (possibly novel / non-microbial) . Provenance — producing organism + taxonomic lineage + literature reference (title, DOI, year). Chemical class — ChemOnt kingdom → superclass → class → subclass → direct_parent (+ molecular framework). Identity cross-refs — PubChem CID/IUPAC, InChIKey, formula, exact mass. Interpretation note (see below). Interpretation Guidance (dereplication logic) InChIKey hit in NPAtlas = structure-level match ⇒ confidently a known microbial NP. Quote the NPAID, organism, and paper. Formula / exact-mass hit(s) only = candidate(s) at the molecular-formula level. Multiple isomers can share one formula and exact mass (e.g. C28H26N4O3 , 466.2005 Da, returns both staurosporine and an ardeemin derivative). Treat these as a ranked candidate list, not an identification — confirm with InChIKey, MS/MS, or NMR before claiming identity. Name hit only = weakest evidence. A name search returns analogs and congeners (searching "staurosporine" returns 5'-hydroxystaurosporine, etc.), not necessarily the exact molecule. Always escalate to an InChIKey check. No NPAtlas hit = not a known microbial natural product. Possible meanings: genuinely novel; a plant/animal/marine metabolite outside NPAtlas scope; or a synthetic/derivatized compound. State which interpretations remain open — do not declare "novel" unconditionally. ClassyFire classified:false = ChemOnt has no cached classification for that exact InChIKey (often because the InChIKey's stereo/charge layer differs from the cached entry, or the compound is new). Report class as unavailable rather than guessing. OPSIN parsed:false = the name was not systematic IUPAC (trade/trivial name); route to PubChem for an InChIKey instead. Worked Example — Staurosporine (trivial name in) Input: staurosporine (a trivial name). OPSIN name=staurosporine → parsed:false (not systematic IUPAC) → fall through to PubChem. PubChem name→CID = 44259 ; properties → MolecularFormula C28H26N4O3 , MW 466.5 , InChIKey HKSZLNNOFSGOKW-FYTWVXJKSA-N . NPAtlas inchikey=HKSZLNNOFSGOKW-FYTWVXJKSA-N → 1 exact hit : NPA014588 Staurosporine , exact_mass 466.2005 . → Known microbial NP . NPAtlas get_compound NPA014588 → producing organism Streptomyces (genus; lineage Bacteria → Actinobacteria → Actinobacteria → Streptomycetales → Streptomycetaceae); reference "X-Ray crystal structure of staurosporine: a new alkaloid from a Streptomyces…" , DOI 10.1039/C39780000800 , 1978. ClassyFire inchikey=HKSZLNNOFSGOKW-FYTWVXJKSA-N → Organic compounds → Organoheterocyclic compounds → Indoles and derivatives → Carbazoles → direct parent Indolocarbazoles ; molecular framework: aromatic heteropolycyclic. Call : Known microbial natural product (NPA014588), an indolocarbazole alkaloid produced by Streptomyces , first reported 1978. Dereplication-logic footnote : the formula C28H26N4O3 (exact mass 466.2005) alone is not unique — NPAtlas formula search returns 2 isomers (staurosporine and 5-N-acetyl-15b-didehydroardeemin). The InChIKey is what pins the identity to staurosporine specifically. An MS feature with only this formula would need MS/MS or NMR to choose between the isomers. Worked Example — Acetylsalicylic acid (systematic name in) Input IUPAC 2-acetyloxybenzoic acid . OPSIN → parsed:true , InChIKey BSYNRYMUTXBXSQ-UHFFFAOYSA-N . NPAtlas inchikey=BSYNRYMUTXBXSQ-... → no microbial NP record ⇒ not a known microbial natural product (it is a semisynthetic drug — consistent with NPAtlas scope). ClassyFire → Organic compounds → Benzenoids → Benzene and substituted derivatives → Benzoic acids and derivatives → direct parent Acylsalicylic acids . Call : Classified into ChemOnt (acylsalicylic acid), but no NPAtlas microbial-NP provenance — illustrating a legitimate "no hit" that is not a novel NP. Limitations (be honest in every report) NPAtlas = microbial NPs only (bacteria + fungi). No plant, animal, or marine-invertebrate metabolites unless a microbial producer was reported. Absence is not proof of novelty. ClassyFire is a cache lookup by InChIKey. classified:false means "not cached for this exact InChIKey", not "unclassifiable". Wrong stereo/charge layers miss the cache. Name search ≠ structure match. NPAtlas/PubChem name searches return synonyms, analogs, and salts. Always confirm identity at the InChIKey level before declaring a compound "known". Formula/exact-mass hits are candidate lists , not identifications — isomers share formulas. Confirm with orthogonal evidence (MS/MS, NMR, InChIKey). OPSIN parses systematic IUPAC names only — trivial/trade names return parsed:false ; route them through PubChem. Search-result records carry origin_organism: null ; provenance requires the NPAtlas_get_compound full record. Out of Scope → route elsewhere General drug/compound identity & ADMET , properties, bioassays → tooluniverse-chemical-compound-retrieval / tooluniverse-small-molecule-discovery . Metabolomics pathway/enrichment analysis → tooluniverse-metabolomics skills. Completeness Checklist Input type classified (name / formula / mass / InChIKey / SMILES). An InChIKey was obtained (OPSIN or PubChem) when starting from a name/SMILES. NPAtlas searched with the most specific key available; full record fetched for any hit (organism + reference). Known/novel call made with the correct caveats (microbial-only scope). ChemOnt class reported from ClassyFire, or marked unavailable if classified:false . Identity cross-referenced in PubChem (CID/formula/InChIKey agree). Interpretation note included (InChIKey vs formula vs name match; meaning of no-hit / classified:false). Limitations stated; every NPAID, organism, DOI, and class came from a live tool call.