Kalimantacin A
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| Category | Antibiotics |
| Catalog number | BBF-01527 |
| CAS | 174513-95-2 |
| Molecular Weight | 548.71 |
| Molecular Formula | C30H48N2O7 |
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Description
Kalimantacin A is originally isolated from Alcaligenes sp. YL-02632S. It has anti-Gram-positive bacteria (including multi-drug resistant bacteria) and some gram-negative bacteria activities.
Specification
| IUPAC Name | (2E,10Z,12E)-20-[(3-carbamoyloxy-2-methylbutanoyl)amino]-19-hydroxy-3,5,15-trimethyl-7-methylidene-17-oxoicosa-2,10,12-trienoic acid |
| Canonical SMILES | CC(CC=CC=CCCC(=C)CC(C)CC(=CC(=O)O)C)CC(=O)CC(CNC(=O)C(C)C(C)OC(=O)N)O |
| InChI | InChI=1S/C30H48N2O7/c1-20(14-22(3)15-23(4)17-28(35)36)12-10-8-7-9-11-13-21(2)16-26(33)18-27(34)19-32-29(37)24(5)25(6)39-30(31)38/h7-9,11,17,21-22,24-25,27,34H,1,10,12-16,18-19H2,2-6H3,(H2,31,38)(H,32,37)(H,35,36)/b8-7-,11-9+,23-17+ |
| InChI Key | GENAAYFYLGYPIQ-JOPGMDTFSA-N |
Properties
| Appearance | White to Light Yellow Powder |
| Antibiotic Activity Spectrum | Gram-positive bacteria; Gram-negative bacteria |
| Boiling Point | 778.2°C at 760 mmHg |
| Density | 1.089 g/cm3 |
Reference Reading
1. Control of β-Branching in Kalimantacin Biosynthesis: Application of 13 C NMR to Polyketide Programming
Paul D Walker, Christopher Williams, Angus N M Weir, Luoyi Wang, John Crosby, Paul R Race, Thomas J Simpson, Christine L Willis, Matthew P Crump Angew Chem Int Ed Engl. 2019 Sep 2;58(36):12446-12450. doi: 10.1002/anie.201905482. Epub 2019 Aug 7.
The presence of β-branches in the structure of polyketides that possess potent biological activity underpins the widespread importance of this structural feature. Kalimantacin is a polyketide antibiotic with selective activity against staphylococci, and its biosynthesis involves the unprecedented incorporation of three different and sequential β-branching modifications. We use purified single and multi-domain enzyme components of the kalimantacin biosynthetic machinery to address in vitro how the pattern of β-branching in kalimantacin is controlled. Robust discrimination of enzyme products required the development of a generalisable assay that takes advantage of 13 C NMR of a single 13 C label incorporated into key biosynthetic mimics combined with favourable dynamic properties of an acyl carrier protein. We report a previously unassigned modular enoyl-CoA hydratase (mECH) domain and the assembly of enzyme constructs and cascades that are able to generate each specific β-branch.
2. Total Synthesis of Kalimantacin A
Jonathan A Davies, Freya M Bull, Paul D Walker, Angus N M Weir, Rob Lavigne, Joleen Masschelein, Thomas J Simpson, Paul R Race, Matthew P Crump, Christine L Willis Org Lett. 2020 Aug 21;22(16):6349-6353. doi: 10.1021/acs.orglett.0c02190. Epub 2020 Aug 10.
The kalimantacins make up a family of hybrid polyketide-nonribosomal peptide-derived natural products that display potent and selective antibiotic activity against multidrug resistant strains of Staphylococcus aureus. Herein, we report the first total synthesis of kalimantacin A, in which three fragments are prepared and then united via Sonogashira and amide couplings. The enantioselective synthetic approach is convergent, unlocking routes to further kalimantacins and analogues for structure-activity relationship studies and clinical evaluation.
3. The Kalimantacin Polyketide Antibiotics Inhibit Fatty Acid Biosynthesis in Staphylococcus aureus by Targeting the Enoyl-Acyl Carrier Protein Binding Site of FabI
Christopher D Fage, Thomas Lathouwers, Michiel Vanmeert, et al. Angew Chem Int Ed Engl. 2020 Jun 22;59(26):10549-10556. doi: 10.1002/anie.201915407. Epub 2020 Apr 14.
The enoyl-acyl carrier protein reductase enzyme FabI is essential for fatty acid biosynthesis in Staphylococcus aureus and represents a promising target for the development of novel, urgently needed anti-staphylococcal agents. Here, we elucidate the mode of action of the kalimantacin antibiotics, a novel class of FabI inhibitors with clinically-relevant activity against multidrug-resistant S. aureus. By combining X-ray crystallography with molecular dynamics simulations, in vitro kinetic studies and chemical derivatization experiments, we characterize the interaction between the antibiotics and their target, and we demonstrate that the kalimantacins bind in a unique conformation that differs significantly from the binding mode of other known FabI inhibitors. We also investigate mechanisms of acquired resistance in S. aureus and identify key residues in FabI that stabilize the binding of the antibiotics. Our findings provide intriguing insights into the mode of action of a novel class of FabI inhibitors that will inspire future anti-staphylococcal drug development.
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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 ╳
