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- Name help_outline isonocardicin A Identifier CHEBI:77633 Charge -2 Formula C23H22N4O9 InChIKeyhelp_outline CTNZOGJNVIFEBA-MOKAZRKYSA-L SMILEShelp_outline N1(C([C@H](C1)NC(/C(/C=2C=CC(OCC[C@@H](C(=O)[O-])[NH3+])=CC2)=N\[O-])=O)=O)[C@@H](C([O-])=O)C3=CC=C(C=C3)O 2D coordinates Mol file for the small molecule Search links Involved in 2 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline nocardicin A Identifier CHEBI:77658 Charge -2 Formula C23H22N4O9 InChIKeyhelp_outline CTNZOGJNVIFEBA-UPSUJEDGSA-L SMILEShelp_outline [NH3+][C@H](CCOc1ccc(cc1)C(=N\[O-])\C(=O)N[C@H]1CN([C@@H](C([O-])=O)c2ccc(O)cc2)C1=O)C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:22792 | RHEA:22793 | RHEA:22794 | RHEA:22795 | |
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| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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Publications
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Mutational analysis of nocK and nocL in the nocardicin a producer Nocardia uniformis.
Kelly W.L., Townsend C.A.
The nocardicins are a family of monocyclic beta-lactam antibiotics produced by the actinomycete Nocardia uniformis subsp. tsuyamanensis ATCC 21806. The most potent of this series is nocardicin A, containing a syn-configured oxime moiety, an uncommon feature in natural products. The nocardicin A bi ... >> More
The nocardicins are a family of monocyclic beta-lactam antibiotics produced by the actinomycete Nocardia uniformis subsp. tsuyamanensis ATCC 21806. The most potent of this series is nocardicin A, containing a syn-configured oxime moiety, an uncommon feature in natural products. The nocardicin A biosynthetic gene cluster was recently identified and found to encode proteins in keeping with nocardicin A production, including the nocardicin N-oxygenase, NocL, in addition to genes of undetermined function, such as nocK, which bears similarities to a broad family of esterases. The latter was hypothesized to be involved in the formation of the critical beta-lactam ring. While previously shown to effect oxidation of the 2'-amine of nocardicin C to provide nocardicin A, it was uncertain whether NocL was the only N-oxidizing enzyme required for nocardicin A biosynthesis. To further detail the role of NocL in nocardicin production in N. uniformis, and to examine the function of nocK, a method for the transformation of N. uniformis protoplasts to inactivate both nocK and nocL was developed and applied. A reliable protocol is reported to achieve both insertional disruption and in trans complementation in this strain. While the nocK mutant still produced nocardicin A at levels near that seen for wild-type N. uniformis, and therefore has no obvious role in nocardicin biosynthesis, the nocL disruptant failed to generate the oxime-containing metabolite. Nocardicin A production was restored in the nocL mutant upon in trans expression of the gene. Furthermore, the nocL mutant accumulated the biosynthetic intermediate nocardicin C, confirming its role as the sole oxime-forming enzyme required for production of nocardicin A. << Less
J. Bacteriol. 187:739-746(2005) [PubMed] [EuropePMC]
This publication is cited by 3 other entries.
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Mutational analysis and characterization of nocardicin C-9' epimerase.
Kelly W.L., Townsend C.A.
The biosynthetic gene cluster for the nocardicin A producer Nocardia uniformis subsp. tsuyamanensis ATCC 21806 was recently identified. Nocardicin A is the most potent of a series of monocyclic beta-lactam antibiotics produced by this organism. Its activity has been attributed to a syn-configured ... >> More
The biosynthetic gene cluster for the nocardicin A producer Nocardia uniformis subsp. tsuyamanensis ATCC 21806 was recently identified. Nocardicin A is the most potent of a series of monocyclic beta-lactam antibiotics produced by this organism. Its activity has been attributed to a syn-configured oxime moiety and a d-homoseryl side chain attached through an unusual ether linkage to the core nocardicin framework. Notably present in the nocardicin biosynthetic gene cluster is nocJ, encoding a protein with sequence similarity to the pyridoxal 5'-phosphate (PLP)-dependent 1-aminocyclopropane-1-carboxylic acid deaminases. Insertional mutagenesis of nocJ abolished nocardicin A production, while the l-homoseryl isomer, isonocardicin A, was still observed. Expression of the disrupted nocJ gene in trans was sufficient to restore production of nocardicin A in the disruption mutant. Heterologous expression, purification, and in vitro characterization of NocJ by UV spectroscopy, cofactor reduction, chiral HPLC analysis of the products and their exchange behavior in deuterium oxide led to confirmation of its role as the PLP-dependent nocardicin C-9' epimerase responsible for interconversion of the nocardicin homoseryl side chain in both nocardicin A with isonocardicin A, and nocardicin C with isonocardicin C. NocJ is the first member of a new class of beta-lactam aminoacyl side chain epimerases, the first two classes being the evolutionarily distinct prokaryotic PLP-dependent isopenicillin N epimerase and the fungal isopenicillin N epimerase two protein system. << Less
J. Biol. Chem. 279:38220-38227(2004) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.