salinosporamide A

CHEBI:48045 EXACT SEEDED

What these status tags mean

Curation status describes a workflow state. SEEDED means the record entered through the source-seeding workflow; it does not imply that no later curation occurred. PROPOSED marks an addition awaiting review; REVIEWED records curator sign-off on identity, structure, filing class and producer claims; DEPRECATED retains a superseded or out-of-scope record. These are workflow decisions, not independently verified human review. Agent-assisted contributions may appear in the record history.

Grounding describes the identifier mapping: EXACT uses an ontology identity asserted by the source; MINTED keeps a local identifier when no defensible ontology identity is available; REVIEW_NEEDED flags an exact structure whose ontology identity needs adjudication. The grounding note retains any unresolved alternatives. These tags do not establish the strength of producer or activity evidence.

A salinosporamide in which the core (1R)-6-oxa-2-azabicyclo[3.2.0]heptane-3,7-dione skeleton is substituted at positions 1, 4, and 5 by (1S)-cyclohex-2-en-1-yl(hydroxy)methyl, 2-chloroethyl, and methyl groups, respectively (the 1R,4R,5S diastereoisomer). A potent proteasome inhibitor, it has attracted interest for potential use in the treatment of various cancers.

Structure

Standard InChIKey	NGWSFRIPKNWYAO-SHTIJGAHSA-N
SMILES	[H][C@](O)([C@@]1([H])CCCC=C1)[C@@]12NC(=O)[C@H](CCCl)[C@]1(C)OC2=O
Stereochemistry	fully defined
Cross-references	npatlas:NPA011013, pubchem:11695330

Filing pathway

Amino acids and peptides — computed by NPClassifier npclassifier.gnps2.org@2026-09-07, which is why it is pinned rather than recomputed. The gene cluster's asserted class is nrps, pks, from MIBiG.

Producer organisms 2

A claim that this taxon makes the compound. The basis says what the evidence addressed — a knockout and a database assertion are not the same claim.

Taxon	Basis	Cluster	Evidence
Salinispora tropica NCBITaxon:168695	BGC_CHARACTERIZED	mibig:BGC0000145	PMID:19590008
Salinispora tropica CNB-440 NCBITaxon:369723	BGC_CHARACTERIZED	mibig:BGC0001041	PMID:19590008

Occurrences 6

Somebody found the compound in this organism and cited it. That is not a claim that the organism makes it, and nothing here promotes one to the other.

Taxon	Source	Reference
Salinispora NCBITaxon:168694	LOTUS	DOI:10.1002/ANIE.200390115
Salinispora tropica NCBITaxon:168695	LOTUS	DOI:10.1002/ANIE.200390115
Salinispora tropica NCBITaxon:168695	LOTUS	DOI:10.1021/JO050511+
Salinispora tropica NCBITaxon:168695	LOTUS	DOI:10.1021/NP0603471
Salinispora tropica NCBITaxon:168695	LOTUS	DOI:10.1021/NP800578E
Salinispora tropica NCBITaxon:168695	CHEBI	PMID:12548698

Biosynthetic gene clusters 2

Accession	Host	Locus evidence	Genome
mibig:BGC0000145	Salinispora tropica NCBITaxon:168695	CLUSTER_DEMONSTRATED	genbank:EF397502.1
mibig:BGC0001041	Salinispora tropica CNB-440 NCBITaxon:369723	CLUSTER_DEMONSTRATED	genbank:CP000667.1

A locus claim and a taxon claim are different questions. Heterologous expression settles the first and leaves the second where the isolation report left it.

Biosynthesis curated

Written by a curator with claim-level evidence on each step; not derived from a source. This is what the rest of the record exists to support.

Step	Enzyme	Reaction	Substrate → product	Evidence
1	SalL UniProtKB:A4X3Q0	RHEA:28110	CHEBI:59789 → CHEBI:47133	DOI:10.1038/nchembio.2007.56
40	SalM 5-chloro-5-deoxy-D-ribose 1-dehydrogenase UniProtKB:A4X3Q1		ungrounded → ungrounded	DOI:10.1073/pnas.0901237106

Step 1: This deliberately curates the Salinispora tropica CNB-440 SalL chlorination of S-adenosyl-L-methionine with chloride to 5'-chloro-5'-deoxyadenosine in the salinosporamide A chloroethylmalonyl-CoA precursor branch. Downstream SalT/SalN formation of 5-chloro-5-deoxy-D-ribose, later conversion to chloroethylmalonyl-CoA, and SalA/B/C assembly remain uncurated.

Step 40: SalM oxidizes 5-chloro-5-deoxy-D-ribose to 5-chloro-5-deoxy-D-ribono-gamma-lactone in the salinosporamide A chloroethylmalonyl-CoA branch. The intervening SalT/SalN conversion of 5'-chloro-5'-deoxyadenosine to 5-chloro-5-deoxy-D-ribose and later steps to chloroethylmalonyl-CoA remain uncurated.

Mechanism & Biosynthesis Overview

Causal graph — biosynthesis 6 nodes, 4 edges

Partial Salinispora tropica CNB-440 salinosporamide A biosynthesis graph for the SalL chlorinase reaction that initiates the chloroethylmalonyl-CoA precursor branch and the SalM oxidation step in that branch.

Subject	Predicate	Object	Notes	Evidence
S-adenosyl-L-methionine zwitterion	is chlorinated by	SalL	RHEA:28110 uses chloride as the co-substrate and releases L-methionine as the co-product.	DOI:10.1038/nchembio.2007.56 DOI:10.1073/pnas.0901237106 https://www.uniprot.org/uniprotkb/A4X3Q0 https://www.ncbi.nlm.nih.gov/protein/ABP53500.1 reference DOI:10.1038/nchembio.2007.56 evidence type PRIMARY_EXPERIMENT snippet SalL, which halogenates S-adenosyl-L-methionine (2) with chloride to generate 5'-chloro-5'-deoxyadenosine (3) and L-methionine (4) notes Eustaquio et al. genetically, biochemically, and structurally characterized Salinispora tropica CNB-440 SalL as the SAM-dependent chlorinase at the start of salinosporamide A chloroethylmalonyl-CoA precursor biosynthesis. reference DOI:10.1073/pnas.0901237106 evidence type PRIMARY_EXPERIMENT snippet S-adenosyl-L-methionine (SAM) is converted to 5'-chloro-5'-deoxyadenosine (5'-ClDA) in a reaction catalyzed by a SAM-dependent chlorinase notes Eustaquio et al. placed SalL upstream of SalM, SalN, SalQ, SalS, SalT, and SalU in the characterized salinosporamide A chloroethylmalonyl-CoA pathway branch. reference https://www.uniprot.org/uniprotkb/A4X3Q0 evidence type DATABASE_ASSERTION retrieved on 2026-09-27 notes Reviewed UniProtKB:A4X3Q0 is Salinispora tropica CNB-440 SalL, gene salL and locus Strop_1026, cross-references EMBL CP000667 protein ABP53500.1, and annotates RHEA:28110 with ChEBI participants CHEBI:17996, CHEBI:47133, CHEBI:57844, and CHEBI:59789. reference https://www.ncbi.nlm.nih.gov/protein/ABP53500.1 evidence type DATABASE_ASSERTION retrieved on 2026-09-27 notes NCBI GenPept ABP53500.1 is the Strop_1026 coding sequence from the Salinispora tropica CNB-440 CP000667.1 salinosporamide A cluster and is sequence-identical to UniProtKB:A4X3Q0.
SalL	forms	5'-chloro-5'-deoxyadenosine	5'-chloro-5'-deoxyadenosine is the first chlorinated intermediate in the salinosporamide A chloroethylmalonyl-CoA precursor branch.	DOI:10.1038/nchembio.2007.56 DOI:10.1073/pnas.0901237106 https://www.uniprot.org/uniprotkb/A4X3Q0 https://www.ncbi.nlm.nih.gov/protein/ABP53500.1 reference DOI:10.1038/nchembio.2007.56 evidence type PRIMARY_EXPERIMENT snippet SalL, which halogenates S-adenosyl-L-methionine (2) with chloride to generate 5'-chloro-5'-deoxyadenosine (3) and L-methionine (4) notes Eustaquio et al. genetically, biochemically, and structurally characterized Salinispora tropica CNB-440 SalL as the SAM-dependent chlorinase at the start of salinosporamide A chloroethylmalonyl-CoA precursor biosynthesis. reference DOI:10.1073/pnas.0901237106 evidence type PRIMARY_EXPERIMENT snippet S-adenosyl-L-methionine (SAM) is converted to 5'-chloro-5'-deoxyadenosine (5'-ClDA) in a reaction catalyzed by a SAM-dependent chlorinase notes Eustaquio et al. placed SalL upstream of SalM, SalN, SalQ, SalS, SalT, and SalU in the characterized salinosporamide A chloroethylmalonyl-CoA pathway branch. reference https://www.uniprot.org/uniprotkb/A4X3Q0 evidence type DATABASE_ASSERTION retrieved on 2026-09-27 notes Reviewed UniProtKB:A4X3Q0 is Salinispora tropica CNB-440 SalL, gene salL and locus Strop_1026, cross-references EMBL CP000667 protein ABP53500.1, and annotates RHEA:28110 with ChEBI participants CHEBI:17996, CHEBI:47133, CHEBI:57844, and CHEBI:59789. reference https://www.ncbi.nlm.nih.gov/protein/ABP53500.1 evidence type DATABASE_ASSERTION retrieved on 2026-09-27 notes NCBI GenPept ABP53500.1 is the Strop_1026 coding sequence from the Salinispora tropica CNB-440 CP000667.1 salinosporamide A cluster and is sequence-identical to UniProtKB:A4X3Q0.
5-chloro-5-deoxy-D-ribose	is oxidized by	SalM	5-chloro-5-deoxy-D-ribose sits downstream of SalL, SalT, and SalN in the proposed pathway; the SalT and SalN steps are not yet represented.	DOI:10.1073/pnas.0901237106 DOI:10.1074/jbc.M110.153833 https://www.uniprot.org/uniprotkb/A4X3Q1 https://www.ncbi.nlm.nih.gov/protein/ABP53501.1 reference DOI:10.1073/pnas.0901237106 evidence type PRIMARY_EXPERIMENT snippet 5'-ClDA is converted to chloroethylmalonyl-CoA in a 7-step route notes Eustaquio et al. characterized the Salinispora tropica CNB-440 sal cluster and placed SalM downstream of SalL, SalT, and SalN in the chloroethylmalonyl-CoA branch for salinosporamide A biosynthesis. reference DOI:10.1074/jbc.M110.153833 evidence type PRIMARY_EXPERIMENT snippet oxidation of 5-chloro-5-deoxy-D-ribose to 5-chloro-5-deoxy-D-ribono-γ-lactone notes Kale et al. amplified S. tropica CNB-440 salM/Strop_1027, heterologously expressed SalM, and used real-time 13C NMR to show NAD+-dependent 5-chloro-5-deoxy-D-ribose oxidation to the gamma-lactone followed by spontaneous lactone hydrolysis. reference https://www.uniprot.org/uniprotkb/A4X3Q1 evidence type DATABASE_ASSERTION retrieved on 2026-09-29 notes UniProtKB:A4X3Q1 is the unreviewed 255 aa Salinispora tropica CNB-440 short-chain dehydrogenase/reductase entry for ordered locus Strop_1027 and cross-references EMBL CP000667 protein ABP53501.1. reference https://www.ncbi.nlm.nih.gov/protein/ABP53501.1 evidence type DATABASE_ASSERTION retrieved on 2026-09-29 notes NCBI GenPept ABP53501.1 is the 255 aa Strop_1027 coding sequence from the Salinispora tropica CNB-440 CP000667.1 chromosome.
SalM	forms	5-chloro-5-deoxy-D-ribono-gamma-lactone	SalM forms the gamma-lactone enzymatically; Kale et al. also observed nonenzymatic hydrolysis to 5-chloro-5-deoxy-D-ribonate.	DOI:10.1073/pnas.0901237106 DOI:10.1074/jbc.M110.153833 https://www.uniprot.org/uniprotkb/A4X3Q1 https://www.ncbi.nlm.nih.gov/protein/ABP53501.1 reference DOI:10.1073/pnas.0901237106 evidence type PRIMARY_EXPERIMENT snippet 5'-ClDA is converted to chloroethylmalonyl-CoA in a 7-step route notes Eustaquio et al. characterized the Salinispora tropica CNB-440 sal cluster and placed SalM downstream of SalL, SalT, and SalN in the chloroethylmalonyl-CoA branch for salinosporamide A biosynthesis. reference DOI:10.1074/jbc.M110.153833 evidence type PRIMARY_EXPERIMENT snippet oxidation of 5-chloro-5-deoxy-D-ribose to 5-chloro-5-deoxy-D-ribono-γ-lactone notes Kale et al. amplified S. tropica CNB-440 salM/Strop_1027, heterologously expressed SalM, and used real-time 13C NMR to show NAD+-dependent 5-chloro-5-deoxy-D-ribose oxidation to the gamma-lactone followed by spontaneous lactone hydrolysis. reference https://www.uniprot.org/uniprotkb/A4X3Q1 evidence type DATABASE_ASSERTION retrieved on 2026-09-29 notes UniProtKB:A4X3Q1 is the unreviewed 255 aa Salinispora tropica CNB-440 short-chain dehydrogenase/reductase entry for ordered locus Strop_1027 and cross-references EMBL CP000667 protein ABP53501.1. reference https://www.ncbi.nlm.nih.gov/protein/ABP53501.1 evidence type DATABASE_ASSERTION retrieved on 2026-09-29 notes NCBI GenPept ABP53501.1 is the 255 aa Strop_1027 coding sequence from the Salinispora tropica CNB-440 CP000667.1 chromosome.

Every edge carries its own citation; an uncited edge is refused by the corpus tests.

Causal graph — bioactivity 4 nodes, 3 edges

Salinosporamide A covalently binds the Saccharomyces cerevisiae 20S proteasome catalytic beta type-1, beta type-2, and beta type-5 subunits.

Subject	Predicate	Object	Notes	Evidence
salinosporamide A	binds	yeast proteasome subunit beta type-1	PDB 2FAK records SA1 salinosporamide A covalently linked to Thr1 of yeast PRE3 chains N and 2, both mapped to UniProtKB:P38624.	DOI:10.1021/ja058320b reference DOI:10.1021/ja058320b evidence type PRIMARY_EXPERIMENT snippet Crystal Structures of Salinosporamide A (NPI-0052) and B (NPI-0047) in Complex with the 20S Proteasome Reveal Important Consequences of beta-Lactone Ring Opening and a Mechanism for Irreversible Binding. notes Groll et al. solved PDB 2FAK as the yeast 20S proteasome covalently bound by salinosporamide A at all six catalytic beta-subunit active sites.
salinosporamide A	binds	yeast proteasome subunit beta type-2	PDB 2FAK records SA1 salinosporamide A covalently linked to Thr1 of yeast PUP1 chains H and V, both mapped to UniProtKB:P25043.	DOI:10.1021/ja058320b reference DOI:10.1021/ja058320b evidence type PRIMARY_EXPERIMENT snippet Crystal Structures of Salinosporamide A (NPI-0052) and B (NPI-0047) in Complex with the 20S Proteasome Reveal Important Consequences of beta-Lactone Ring Opening and a Mechanism for Irreversible Binding. notes Groll et al. solved PDB 2FAK as the yeast 20S proteasome covalently bound by salinosporamide A at all six catalytic beta-subunit active sites.
salinosporamide A	binds	yeast proteasome subunit beta type-5	PDB 2FAK records SA1 salinosporamide A covalently linked to Thr1 of yeast PRE2 chains K and Y, both mapped to UniProtKB:P30656.	DOI:10.1021/ja058320b reference DOI:10.1021/ja058320b evidence type PRIMARY_EXPERIMENT snippet Crystal Structures of Salinosporamide A (NPI-0052) and B (NPI-0047) in Complex with the 20S Proteasome Reveal Important Consequences of beta-Lactone Ring Opening and a Mechanism for Irreversible Binding. notes Groll et al. solved PDB 2FAK as the yeast 20S proteasome covalently bound by salinosporamide A at all six catalytic beta-subunit active sites.

Every edge carries its own citation; an uncited edge is refused by the corpus tests.

Explore across X-Mech

AntibioticMech (salinosporamide A) ↗ MediaIngredientMech (CHEBI:48045) ↗ TaxonMech: Salinispora tropica (NCBITaxon:168695) ↗ TaxonMech: Salinispora tropica CNB-440 (NCBITaxon:369723) ↗ PathwayMech (mibig:BGC0000145) ↗ PathwayMech (mibig:BGC0001041) ↗

Open questions 1

shared-structure — This structure is reported by more than one MIBiG entry: BGC0000145, BGC0001041. Confirm they describe the same compound rather than an upstream cross-reference error.

Provenance

Source concept	Source	Version
BGC0000145	MIBIG	5
BGC0001041	MIBIG	4
CHEBI:48045	CHEBI	3-star

This page is generated from data/natural_products/amino_acids_and_peptides/salinosporamide-a.yaml, which is generated from the committed inventories. Neither is edited by hand.