Nocardicin A
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| Category | Antibiotics |
| Catalog number | BBF-02607 |
| CAS | 39391-39-4 |
| Molecular Weight | 500.46 |
| Molecular Formula | C23H24N4O9 |
| Purity | 95% |
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Description
Nocardicin A is originally isolated from Nocardia uniformis subsp. tsugamanensis. Nocardicin A has antibacterial action, but it only has strong antibacterial activity against Octococcus, Proteus and Shigella soontii.
Specification
| Synonyms | Isonocardicin A; (αR,3S)-3-[[(2Z)-2-[4-[(3R)-3-Amino-3-carboxypropoxy]phenyl]-2-(hydroxyimino)acetyl]amino]-α-(4-hydroxyphenyl)-2-oxo-1-azetidineacetic Acid |
| IUPAC Name | (2R)-2-amino-4-[4-[(E)-C-[[(3S)-1-[carboxy-(4-hydroxyphenyl)methyl]-2-oxoazetidin-3-yl]carbamoyl]-N-hydroxycarbonimidoyl]phenoxy]butanoic acid |
| Canonical SMILES | C1C(C(=O)N1C(C2=CC=C(C=C2)O)C(=O)O)NC(=O)C(=NO)C3=CC=C(C=C3)OCCC(C(=O)O)N |
| InChI | InChI=1S/C23H24N4O9/c24-16(22(31)32)9-10-36-15-7-3-12(4-8-15)18(26-35)20(29)25-17-11-27(21(17)30)19(23(33)34)13-1-5-14(28)6-2-13/h1-8,16-17,19,28,35H,9-11,24H2,(H,25,29)(H,31,32)(H,33,34)/b26-18+/t16-,17+,19?/m1/s1 |
| InChI Key | CTNZOGJNVIFEBA-DESWKMRBSA-N |
Properties
| Application | A β-lactam antibiotic. |
| Boiling Point | 591.34°C at 760 mmHg |
| Melting Point | 214-216°C |
| Density | 1.436 g/cm3 |
Reference Reading
1.Non-ribosomal propeptide precursor in nocardicin A biosynthesis predicted from adenylation domain specificity dependent on the MbtH family protein NocI.
Davidsen JM1, Bartley DM, Townsend CA. J Am Chem Soc. 2013 Feb 6;135(5):1749-59. doi: 10.1021/ja307710d. Epub 2013 Jan 18.
Nocardicin A is a monocyclic β-lactam isolated from the actinomycete Nocardia uniformis that shows moderate antibiotic activity against a broad spectrum of gram-negative bacteria. The monobactams are of renewed interest due to emerging gram-negative strains resistant to clinically available penicillins and cephalosporins. Like isopenicillin N, nocardicin A has a tripeptide core of non-ribosomal origin. Paradoxically, the nocardicin A gene cluster encodes two non-ribosomal peptide synthetases (NRPSs), NocA and NocB, predicted to encode five modules pointing to a pentapeptide precursor in nocardicin A biosynthesis, unless module skipping or other nonlinear reactions are occurring. Previous radiochemical incorporation experiments and bioinformatic analyses predict the incorporation of p-hydroxy-L-phenylglycine (L-pHPG) into positions 1, 3, and 5 and L-serine into position 4. No prediction could be made for position 2. Multidomain constructs of each module were heterologous expressed in Escherichia coli for determination of the adenylation domain (A-domain) substrate specificity using the ATP/PPi exchange assay.
2.In vivo characterization of nonribosomal peptide synthetases NocA and NocB in the biosynthesis of nocardicin A.
Davidsen JM1, Townsend CA. Chem Biol. 2012 Feb 24;19(2):297-306. doi: 10.1016/j.chembiol.2011.10.020.
Two nonribosomal peptide synthetases (NRPS), NocA and NocB, together comprising five modules, are essential for the biosynthesis of the D,L,D configured tripeptide backbone of the monocyclic β-lactam nocardicin A. We report a double replacement gene strategy in which point mutations were engineered in the two encoding NRPS genes without disruption of the nocABC operon by placing selective markers in adjacent genes. A series of mutants was constructed to inactivate the thiolation (T) domain of each module and to evaluate an HHxxxDR catalytic motif in NocA and an atypical extended histidine motif in NocB. The loss of nocardicin A production in each of the T domain mutants indicates that all five modules are essential for its biosynthesis. Conversely, production of nocardicin A was not affected by mutation of the NocB histidine motif or the R828G mutation in NocA.
3.Identification and characterization of NocR as a positive transcriptional regulator of the beta-lactam nocardicin A in Nocardia uniformis.
Davidsen JM1, Townsend CA. J Bacteriol. 2009 Feb;191(3):1066-77. doi: 10.1128/JB.01833-07. Epub 2008 Nov 21.
Nocardicin A is a monocyclic beta-lactam isolated from the actinomycete Nocardia uniformis, which shows moderate activity against a broad spectrum of gram-negative bacteria. Within the biosynthetic gene cluster of nocardicin A, nocR encodes a 583-amino-acid protein with high similarity to a class of transcriptional regulators known as streptomyces antibiotic regulatory proteins. Insertional inactivation of this gene resulted in a mutant showing morphology and growth characteristics similar to the wild type, but one that did not produce detectable levels of nocardicin A or the early precursor p-hydroxybenzoyl formate. Similar disruptions of nocD, nocE, and nocO yielded mutants that maintained production of nocardicin A at levels similar to the wild-type strain. In trans complementation of the nocR::apr mutant partially restored the wild-type phenotype. Transcriptional analysis of the nocR::apr mutant using reverse transcription-PCR found an absence of mRNA transcripts for the early-stage nocardicin A biosynthetic genes.
4.Mutational analysis of nocK and nocL in the nocardicin a producer Nocardia uniformis.
Kelly WL1, Townsend CA. J Bacteriol. 2005 Jan;187(2):739-46.
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.
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Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
