Thiotetromycin is isolated from Streptomyces sp. OM-674 discovered in the course of the screening for antibacterial antibiotics. The antibiotic was found to be a specific inhibitor of type II fatty acid synthase. In order to search acyl-CoA synthetase inhibitors, a kind of yeast, Candida lipolytica, was utilized as test organism for the primary screening. Four structurally related compounds named triacsin were isolated from Streptomyces sp. SK-1894 as a specific inhibitor of acyl-CoA synthetase I of C. lipolytica. Further biochemical studies revealed that triacsins inhibit acyl-CoA synthetases from widely different sources. The inhibition is competitive with respect to long chain fatty acids. The common N-hydroxytriazene moiety of triacsins is essential for inhibition. To discover inhibitors of mevalonate biosynthesis, Vero cells were used as test organism for the screening. A beta-lactone 1233A(F-244) isolated from Scopulariopsis sp. F-244 was demonstrated to inhibit mevalonate biosynthesis with assays using cell and enzyme systems. Further studies demonstrated that the compound inhibits 3-hydroxy-3-methylglutaryl (HMG)-CoA synthase specifically and irreversibly. The geometry of the (2R, 3R)-beta-lactone ring in the structure is essential for specific inhibition against the enzyme.
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| Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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| Site | Modification | Modifier | Source | Reference |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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| Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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| Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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