Celesticetin A
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| Category | Antibiotics |
| Catalog number | BBF-00501 |
| CAS | 2520-21-0 |
| Molecular Weight | 528.61 |
| Molecular Formula | C24H36N2O9S |
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Description
It is produced by the strain of Streptomyces caelestis NRRL 2418. It has anti-gram-positive bacterial activity.
Specification
| Synonyms | Celesticetin; CHEBI:156421; D-erythro-a-D-galacto-Octopyranoside, 2-[(2-hydroxybenzoyl)oxy]ethyl6,8-dideoxy-7-O-methyl-6-[[[(2S)-1-methyl-2-pyrrolidinyl]carbonyl]amino]-1-thio-; 1-Methyl-L-prolin-{(1R,2R)-2-methoxy-1-[(2R)-3c,4c,5t-trihydroxy-6t-(2-salicyloyloxy-aethylmercapto)-tetrahydro-pyran-2r-yl]-propylamid}; U-5524 |
| IUPAC Name | 2-[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-[2-methoxy-1-[[(2S)-1-methylpyrrolidine-2-carbonyl]amino]propyl]oxan-2-yl]sulfanylethyl 2-hydroxybenzoate |
| Canonical SMILES | CC(C(C1C(C(C(C(O1)SCCOC(=O)C2=CC=CC=C2O)O)O)O)NC(=O)C3CCCN3C)OC |
| InChI | InChI=1S/C24H36N2O9S/c1-13(33-3)17(25-22(31)15-8-6-10-26(15)2)21-19(29)18(28)20(30)24(35-21)36-12-11-34-23(32)14-7-4-5-9-16(14)27/h4-5,7,9,13,15,17-21,24,27-30H,6,8,10-12H2,1-3H3,(H,25,31)/t13?,15-,17?,18-,19+,20+,21+,24+/m0/s1 |
| InChI Key | VMSQKUCYEMOKMM-AFJAYNRNSA-N |
Properties
| Boiling Point | 748.7 °C at 760 mmHg |
| Density | 1.39 g/cm3 |
| Solubility | Soluble in Chloroform, Water |
Reference Reading
1. Lincosamide synthetase--a unique condensation system combining elements of nonribosomal peptide synthetase and mycothiol metabolism
Jiri Janata, Stanislav Kadlcik, Marketa Koberska, Dana Ulanova, Zdenek Kamenik, Petr Novak, Jan Kopecky, Jitka Novotna, Bojana Radojevic, Kamila Plhackova, Radek Gazak, Lucie Najmanova PLoS One. 2015 Mar 5;10(3):e0118850. doi: 10.1371/journal.pone.0118850. eCollection 2015.
In the biosynthesis of lincosamide antibiotics lincomycin and celesticetin, the amino acid and amino sugar units are linked by an amide bond. The respective condensing enzyme lincosamide synthetase (LS) is expected to be an unusual system combining nonribosomal peptide synthetase (NRPS) components with so far unknown amino sugar related activities. The biosynthetic gene cluster of celesticetin was sequenced and compared to the lincomycin one revealing putative LS coding ORFs shared in both clusters. Based on a bioassay and production profiles of S. lincolnensis strains with individually deleted putative LS coding genes, the proteins LmbC, D, E, F and V were assigned to LS function. Moreover, the newly recognized N-terminal domain of LmbN (LmbN-CP) was also assigned to LS as a NRPS carrier protein (CP). Surprisingly, the homologous CP coding sequence in celesticetin cluster is part of ccbZ gene adjacent to ccbN, the counterpart of lmbN, suggesting the gene rearrangement, evident also from still active internal translation start in lmbN, and indicating the direction of lincosamide biosynthesis evolution. The in vitro test with LmbN-CP, LmbC and the newly identified S. lincolnensis phosphopantetheinyl transferase Slp, confirmed the cooperation of the previously characterized NRPS A-domain LmbC with a holo-LmbN-CP in activation of a 4-propyl-L-proline precursor of lincomycin. This result completed the functional characterization of LS subunits resembling NRPS initiation module. Two of the four remaining putative LS subunits, LmbE/CcbE and LmbV/CcbV, exhibit low but significant homology to enzymes from the metabolism of mycothiol, the NRPS-independent system processing the amino sugar and amino acid units. The functions of particular LS subunits as well as cooperation of both NRPS-based and NRPS-independent LS blocks are discussed. The described condensing enzyme represents a unique hybrid system with overall composition quite dissimilar to any other known enzyme system.
2. Adaptation of an L-proline adenylation domain to use 4-propyl-L-proline in the evolution of lincosamide biosynthesis
Stanislav Kadlčík, Tomáš Kučera, Dominika Chalupská, Radek Gažák, Markéta Koběrská, Dana Ulanová, Jan Kopecký, Eva Kutejová, Lucie Najmanová, Jiří Janata PLoS One. 2013 Dec 27;8(12):e84902. doi: 10.1371/journal.pone.0084902. eCollection 2013.
Clinically used lincosamide antibiotic lincomycin incorporates in its structure 4-propyl-L-proline (PPL), an unusual amino acid, while celesticetin, a less efficient related compound, makes use of proteinogenic L-proline. Biochemical characterization, as well as phylogenetic analysis and homology modelling combined with the molecular dynamics simulation were employed for complex comparative analysis of the orthologous protein pair LmbC and CcbC from the biosynthesis of lincomycin and celesticetin, respectively. The analysis proved the compared proteins to be the stand-alone adenylation domains strictly preferring their own natural substrate, PPL or L-proline. The LmbC substrate binding pocket is adapted to accommodate a rare PPL precursor. When compared with L-proline specific ones, several large amino acid residues were replaced by smaller ones opening a channel which allowed the alkyl side chain of PPL to be accommodated. One of the most important differences, that of the residue corresponding to V306 in CcbC changing to G308 in LmbC, was investigated in vitro and in silico. Moreover, the substrate binding pocket rearrangement also allowed LmbC to effectively adenylate 4-butyl-L-proline and 4-pentyl-L-proline, substrates with even longer alkyl side chains, producing more potent lincosamides. A shift of LmbC substrate specificity appears to be an integral part of biosynthetic pathway adaptation to the PPL acquisition. A set of genes presumably coding for the PPL biosynthesis is present in the lincomycin--but not in the celesticetin cluster; their homologs are found in biosynthetic clusters of some pyrrolobenzodiazepines (PBD) and hormaomycin. Whereas in the PBD and hormaomycin pathways the arising precursors are condensed to another amino acid moiety, the LmbC protein is the first functionally proved part of a unique condensation enzyme connecting PPL to the specialized amino sugar building unit.
3. Characterization of N-demethyllincosamide methyltransferases LmbJ and CcbJ
Lucie Najmanová, Eva Kutejová, Jan Kadlec, Marek Polan, Jana Olšovská, Oldřich Benada, Jitka Novotná, Zdeněk Kameník, Petr Halada, Jacob Bauer, Jiří Janata Chembiochem. 2013 Nov 25;14(17):2259-62. doi: 10.1002/cbic.201300389. Epub 2013 Oct 25.
Chemical diversity: Two SAM-dependent N-methyltransferases-LmbJ from the biosynthesis of the antibiotic lincomycin and CcbJ from celesticetin biosynthesis-have been characterized and compared. Both tested enzymes form multimers and are able to utilize N-demethyllincomycin, the natural substrate of LmbJ, with comparable efficiency.
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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 ╳
