novobiocin

CHEBI:28368 ·resolve ·ANTIBACTERIAL ·EXACT REVIEWED

A coumarin-derived antibiotic obtained from Streptomyces niveus. — ChEBI

Classification

aminocoumarin antibioticARO:3000103

Strictly broader compounds or drug classes this molecule belongs to.

Label unavailable CHEBI:23003
Label unavailable CHEBI:25698
Label unavailable CHEBI:29347
Label unavailable CHEBI:33853
Label unavailable CHEBI:35313
Label unavailable CHEBI:37912
Label unavailable CHEBI:63367
aminocoumarin antibiotic ARO:3000103

Chemical structure

Computed structure properties
Molecular formula	C31H36N2O11
Charge	0
Average mass	612.632 Da
Monoisotopic mass	612.23191 Da
Source	ChEBI
InChIKey	YJQPYGGHQPGBLI-KGSXXDOSSA-N

SMILES

CO[C@@H]1[C@@H](OC(N)=O)[C@@H](O)[C@H](Oc2ccc3c(O)c(NC(=O)c4ccc(O)c(CC=C(C)C)c4)c(=O)oc3c2C)OC1(C)C

InChI

InChI=1S/C31H36N2O11/c1-14(2)7-8-16-13-17(9-11-19(16)34)27(37)33-21-22(35)18-10-12-20(15(3)24(18)42-28(21)38)41-29-23(36)25(43-30(32)39)26(40-6)31(4,5)44-29/h7,9-13,23,25-26,29,34-36H,8H2,1-6H3,(H2,32,39)(H,33,37)/t23-,25+,26-,29-/m1/s1

Also called

novobiocina (INN)— chebi
novobiocine (INN)— chebi
novobiocinum (INN)— chebi
N-{7-[(3-O-carbamoyl-6-deoxy-5-methyl-4-O-methyl-β-D-gulopyranosyl)oxy]-4-hydroxy-8-methyl-2-oxo-2H-chromen-3-yl}-4-hydroxy-3-(3-methylbut-2-en-1-yl)benzamide (EXACT_SYNONYM)— chebi
Novobiocin (EXACT_SYNONYM)— chebi
cathomycin (EXACT_SYNONYM)— aro
streptonivicin (EXACT_SYNONYM)— aro

Cross-references

Identifiers for this same structure in other resources. An accession that lands on two different structures in this corpus is withheld from both rather than shown here, since it names at most one of them.

Drug registries

Identifiers that name a drug rather than a structure. One of these can cover a parent compound, its salts and its stereoisomers, which this corpus keeps as separate records, so it is not an equivalence of structure.

Patents and articles

Documents about this compound. A patent covers a class and an article covers a topic; neither identifies a structure.

Activity roles

Every antimicrobial role a source asserts for this compound — the unreduced evidence behind its antimicrobial_class.

antimicrobial agent CHEBI:33281
antibacterial agent CHEBI:33282

Source concepts

Every upstream concept that resolved to this record. The merge is the product: this is what shows ChEBI and CARD are describing the same structure.

Upstream concepts merged into this record
Source	Native ID	Label	Minted CURIE	Version
ARO	`ARO:3000111`	novobiocin	`antibioticmech:aro-de163f36e9`	2026-08-30
CHEBI	`CHEBI:28368`	novobiocin	`antibioticmech:chebi-e739e10a6f`	2026-08-30

Molecular targets

The molecular entity or process this compound acts on. Each target carries evidence — this is a mechanistic claim, not a classification.

aminocoumarin sensitive parE PROTEIN DIRECT_BINDING_TARGET

ARO:3000023

CARD/ARO database assertion; target organism, strain, and assay are not specified. Topoisomerase IV subunit asserted as the aminocoumarin-sensitive target. Evidence status: PRIMARY_EVIDENCE_NEEDED. Source: CARD_ARO 2026-08-30 (retrieved 2026-08-30).

ARO:3000023 (CARD/ARO asserts targeted_by_antibiotic ARO:3000111 (novobiocin); database assertion, not a primary citation.)

antibiotic sensitive DNA topoisomerase subunit gyrB PROTEIN DIRECT_BINDING_TARGET

ARO:3000734

CARD/ARO database assertion; target organism, strain, and assay are not specified. ARO explicitly describes ligand binding to gyrase subunit B. Evidence status: PRIMARY_EVIDENCE_NEEDED. Source: CARD_ARO 2026-08-30 (retrieved 2026-08-30).

ARO:3000734 (CARD/ARO asserts targeted_by_antibiotic ARO:3000111 (novobiocin); database assertion, not a primary citation.)

aminocoumarin sensitive parY PROTEIN DIRECT_BINDING_TARGET

ARO:3003253

CARD/ARO database assertion; target organism, strain, and assay are not specified. ParY is asserted as the aminocoumarin-sensitive subunit. Evidence status: PRIMARY_EVIDENCE_NEEDED. Source: CARD_ARO 2026-08-30 (retrieved 2026-08-30).

ARO:3003253 (CARD/ARO asserts targeted_by_antibiotic ARO:3000111 (novobiocin); database assertion, not a primary citation.)

aminocoumarin sensitive gyrB PROTEIN DIRECT_BINDING_TARGET

ARO:3003260

CARD/ARO database assertion; target organism, strain, and assay are not specified. GyrB is asserted as the aminocoumarin-sensitive subunit. Evidence status: PRIMARY_EVIDENCE_NEEDED. Source: CARD_ARO 2026-08-30 (retrieved 2026-08-30).

ARO:3003260 (CARD/ARO asserts targeted_by_antibiotic ARO:3000111 (novobiocin); database assertion, not a primary citation.)

DNA gyrase B 24-kDa fragment PROTEIN MEASURED_TARGET_ASSOCIATION

Isothermal titration and differential scanning calorimetry compared novobiocin and related coumarins binding the gyrase fragment; only clorobiocin and a synthetic analogue were crystallized in the study. Evidence status: PRIMARY_EVIDENCE. Source: PRIMARY_LITERATURE 2002-06 (retrieved 2026-09-02).

Organism-specific examples
Protein	Gene	Organism	Entry
DNA gyrase subunit B `UniProtKB:P0AES6` Full-length E. coli K-12 GyrB precursor of the 24-kDa N-terminal ATP-binding fragment crystallized with novobiocin (PMID:12044152; PDB 1KIJ).	gyrB	Escherichia coli (strain K12) `NCBITaxon:83333`	REVIEWED

PMID:12044152 (Primary coumarin-gyrase thermodynamics and structure study (DOI:10.1021/bi0159837).)

Mechanism summary

Mode of action: NUCLEIC_ACID_SYNTHESIS_INHIBITION host shared target — CURATOR: PMID:12044152 measured novobiocin binding thermodynamics against the 24-kDa DNA-gyrase fragment and found clorobiocin bound more strongly. The reported cocrystals contained clorobiocin or a synthetic analogue, not novobiocin, so they support coumarin structure-affinity interpretation but are not novobiocin-bound structures.

Resistance mechanisms

15 source-backed resistance determinants or associations, with ARO grounding where reported. Grouped by reported mechanism type.

ANTIBIOTIC_EFFLUX 7

ANTIBIOTIC_EFFLUX
Determinant	ARO ID	Organism	Gene families	Evidence
LptD	ARO:3005059	not organism-specific	—	ARO:3005059 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000111 (novobiocin); database assertion, not a primary citation.)
MdtABC-TolC	ARO:3000787	not organism-specific	—	ARO:3000787 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000111 (novobiocin); database assertion, not a primary citation.)
MexAB-OprM	ARO:3000386	not organism-specific	—	ARO:3000386 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000111 (novobiocin); database assertion, not a primary citation.)
MexCD-OprJ	ARO:3000797	not organism-specific	—	ARO:3000797 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000111 (novobiocin); database assertion, not a primary citation.)
MuxABC-OpmB	ARO:3004076	not organism-specific	—	ARO:3004076 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000111 (novobiocin); database assertion, not a primary citation.)
abeS	ARO:3000768	not organism-specific	—	ARO:3000768 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000111 (novobiocin); database assertion, not a primary citation.)
novA	ARO:3002522	not organism-specific	—	ARO:3002522 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000111 (novobiocin); database assertion, not a primary citation.)

ANTIBIOTIC_TARGET_ALTERATION 7

ANTIBIOTIC_TARGET_ALTERATION
Determinant	ARO ID	Organism	Gene families	Evidence
Bartonella bacilliformis gyrB conferring resistance to aminocoumarin	ARO:3003302	not organism-specific	—	ARO:3003302 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000111 (novobiocin); database assertion, not a primary citation.)
Escherichia coli gyrB conferring resistance to aminocoumarin	ARO:3003303	not organism-specific	—	ARO:3003303 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000111 (novobiocin); database assertion, not a primary citation.)
Staphylococcus aureus gyrB conferring resistance to aminocoumarin	ARO:3003301	not organism-specific	—	ARO:3003301 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000111 (novobiocin); database assertion, not a primary citation.)
Staphylococcus aureus parE conferring resistance to aminocoumarin	ARO:3003314	not organism-specific	—	ARO:3003314 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000111 (novobiocin); database assertion, not a primary citation.)
Streptomyces rishiriensis parY mutant conferring resistance to aminocoumarin	ARO:3003318	not organism-specific	—	ARO:3003318 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000111 (novobiocin); database assertion, not a primary citation.)
aminocoumarin-resistant alaS	ARO:3003830	not organism-specific	—	ARO:3003830 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000111 (novobiocin); database assertion, not a primary citation.)
aminocoumarin-resistant cysB	ARO:3003840	not organism-specific	—	ARO:3003840 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000111 (novobiocin); database assertion, not a primary citation.)

UNKNOWN 1

UNKNOWN
Determinant	ARO ID	Organism	Gene families	Evidence
ParYR-associated reduced susceptibility to novobiocin The comparison concerns laboratory derivatives of the TK24 background, not native-donor susceptibility or species-wide resistance. NCBITaxon:457428 denotes the TK24 background, not the experimental derivative. The reported donor is Streptomyces rishiriensis DSM 40489. UniProtKB:Q83WB8 is reference-only (entry version 120, sequence version 2); the archive succession does not establish the exact experimental allele. The 2003 study leaves ParY enzymatic function unresolved. No induced point mutant, clinical category, numerical AST, derivative TaxID or experimental genome is assigned. Compound scope follows the source's named structure in Figure 1A, not independent re-identification of the tested preparation.	—	Streptomyces lividans `NCBITaxon:1916`	parYR	PMID:12604514 (Relevant publisher-indexed Results text was inspected before the later article request returned 403; native Figure 1A was visually inspected separately. Native Table 2 and complete paper review remain open.) Qualitative source-reported laboratory-host growth comparison

Causal graphs

Evidence-backed mechanism graphs: how the compound reaches its target, what the target does, and how the effect propagates to growth inhibition or death.

Novobiocin inhibits GyrB ATPase-dependent DNA supercoiling MECHANISTIC

Novobiocin binds the amino-terminal coumarin-binding region of bacterial DNA gyrase subunit GyrB, competitively inhibits its ATPase activity, and blocks ATP-dependent DNA supercoiling by gyrase.

Nodes — novobiocin_gyrb_atpase_inhibition
Node	Label	Type	Grounding
`novobiocin`	novobiocin	COMPOUND	`CHEBI:28368`
`gyrb`	bacterial DNA gyrase subunit GyrB Examples: DNA gyrase subunit B (gyrB) `UniProtKB:P0AES6`, Escherichia coli (strain K12) `NCBITaxon:83333` REVIEWED — ATP-binding GyrB subunit whose N-terminal 24-kDa domain binds novobiocin at the ATPase site (PMID:8386298; PMID:12044152; E. coli K-12 reference context).	GENE_OR_PROTEIN	`ARO:3000734`
`gyrb_coumarin_binding_domain`	GyrB amino-terminal coumarin-binding domain	STATE	REVIEWED_LABEL_ONLY
`gyrb_atpase_activity`	GyrB ATPase activity	MOLECULAR_FUNCTION	REVIEWED_LABEL_ONLY
`dna_supercoiling`	ATP-dependent DNA supercoiling	BIOLOGICAL_PROCESS	REVIEWED_LABEL_ONLY
`dna_topology_control`	bacterial DNA topology control	BIOLOGICAL_PROCESS	REVIEWED_LABEL_ONLY

Edges — novobiocin_gyrb_atpase_inhibition
Subject	Predicate	Object	Evidence
`novobiocin`	binds	`gyrb_coumarin_binding_domain`	PMID:8065258 (Gilbert and Maxwell mapped coumarin-drug binding to a 24 kDa N-terminal GyrB subdomain.)
`gyrb`	contains	`gyrb_coumarin_binding_domain`	PMID:8065258 (The GyrB 24 kDa amino-terminal fragment retained coumarin-drug binding.)
`gyrb`	enables	`gyrb_atpase_activity`	PMID:6269086 (Purified GyrB carried the ATPase activity inhibited competitively by novobiocin and related coumarins.)
`novobiocin`	inhibits	`gyrb_atpase_activity`	PMID:6269086 (The affinity-purified GyrB study characterized novobiocin as a competitive inhibitor of GyrB ATPase activity.)
`gyrb_atpase_activity`	supports	`dna_supercoiling`	PMID:794878 (Gellert and colleagues showed novobiocin inhibits ATP-dependent DNA supercoiling catalyzed by purified DNA gyrase.)
`dna_supercoiling`	supports	`dna_topology_control`	PMID:794878 (The purified gyrase assays connect GyrB ATPase inhibition to loss of DNA supercoiling.)

Record-level evidence

PMID:12044152 (Primary novobiocin-versus-clorobiocin gyrase-binding thermodynamics study.)

Curation history

SEEDED_FROM_SOURCES 2026-08-30 · seed_from_sources
Seeded from data/raw/ inventories (ARO, CHEBI)
RESEEDED_FROM_SOURCES 2026-08-30 · seed_from_sources
Re-seeded from updated data/raw/ inventories
RESEEDED_FROM_SOURCES 2026-08-30 · seed_from_sources
Re-seeded from updated data/raw/ inventories
RESEEDED_FROM_SOURCES 2026-08-31 · seed_from_sources
Re-seeded from updated data/raw/ inventories
REVIEWED 2026-09-03 · codex · LLM-assisted
Verified exact ChEBI/CARD identity, structure, roles, class, and retained CARD target/resistance provenance; curator-confirmed gyrase-mediated nucleic-acid-synthesis inhibition and added the measured GyrB association without attributing another coumarin's cocrystal to novobiocin.
CURATED_CAUSAL_GRAPH 2026-09-04 · codex · LLM-assisted
Added a PMID-supported causal graph for novobiocin inhibition of GyrB ATPase-dependent DNA supercoiling.
RESEEDED_FROM_SOURCES 2026-09-10 · seed_from_sources
Re-seeded from updated data/raw/ inventories
CURATED_RESISTANCE_EVIDENCE 2026-10-10 · codex · LLM-assisted
Added one qualitative primary-backed ParYR-associated host susceptibility finding; preserved donor/host/reference distinctions and all existing source slices. No exact allele, numerical AST or genome assigned. Whole-record review remains open.
CURATED_UNIPROT_PROTEIN_EXAMPLES 2026-10-18 · antigravity · LLM-assisted
Added curated E. coli K-12 GyrB (P0AES6) UniProtKB protein examples on the novobiocin_gyrb_atpase_inhibition gyrb causal graph node and the PRIMARY_LITERATURE DNA gyrase B 24-kDa fragment molecular target.

Provenance

Seeded by scripts/seed_from_sources.py from the committed inventories in data/raw/. View the record (YAML).

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