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Natural product
Phoslactomycin B
Другие языки:

    Phoslactomycin B

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    Phoslactomycin B
    Phospholactomycin B.png
    Names
    Preferred IUPAC name
    (1E,3R,4R,6R,7Z,9Z)-3-(2-Aminoethyl)-10-cyclohexyl-1-[(2S,3S)-3-ethyl-6-oxo-3,6-dihydro-2H-pyran-2-yl]-3,6-dihydroxydeca-1,7,9-trien-4-yl dihydrogen phosphate
    Other names
    2H-Pyran-2-one, 6-(3-(2-aminoethyl)-10-cyclohexyl-3,6-dihydroxy-4-(phosphonooxy)-1,7,9-decatrienyl)-5-ethyl-5,6-dihydro-
    Identifiers
    3D model (JSmol)
    ChEBI
    ChemSpider
    KEGG
    PubChem CID
    • InChI=1S/C25H40NO8P/c1-2-20-12-13-24(28)33-22(20)14-15-25(29,16-17-26)23(34-35(30,31)32)18-21(27)11-7-6-10-19-8-4-3-5-9-19/h6-7,10-15,19-23,27,29H,2-5,8-9,16-18,26H2,1H3,(H2,30,31,32)/b10-6-,11-7-,15-14+/t20-,21-,22-,23+,25-/m0/s1
      Key: GAIPQMSJLNWRGC-MZAVDHTQSA-N
    • CC[C@H]1C=CC(=O)O[C@H]1/C=C/[C@](CCN)([C@@H](C[C@H](/C=C\C=C/C2CCCCC2)O)OP(=O)(O)O)O
    Properties
    C25H40NO8P
    Molar mass 513.568 g·mol−1
    Density 1.3
    Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

    Phoslactomycin (PLM) is a natural product from the isolation of Streptomyces species. This is an inhibitor of the protein serine/threonine phosphatase which is the protein phosphate 2A (PP2A). The PP2A involves the growth factor of the cell such as to induce the formation of mitogen-activated protein interaction and playing a role in cell division and signal transduction. Therefore, PLM is used for the drug that prevents the tumor, cancer, or bacteria. There are nowsaday has 7 kinds of different PLM from PLM A to PLM G which differ the post-synthesis from the biosynthesis of PLM.

    Phoslactomycin B (PLM B) is the product of the post synthase of the biosynthesis of phoslactomycin and the intermediate to produce the other PLMs. The biosynthesis of phoslactomycin belongs to type I polyketide synthase (PKS). A polyketide is are characterized by a macrocyclic lactone and is produced by bacteria and fungi. From the PLM B, there are many articles wrote about the synthesis of different PLM A through PLM G.

    PHOSLACTOMYCIN B
    Phospholactomycin B.png
    Chemical and physical data
    Formula
    Vapour pressure 0.0±5.7 mmHg at 25 °C
    Polarizability 54.3±0.5 10−24cm3
    Biology Organism
    Kingdom Bacteria
    Family Streptomycetaceae
    Identify Information
    Classification OXIDOREDUCTASE
    RDF Unique Identifier
    		 C060449
    KNApSAcK CID C00017683
    ChemBL PMID 23790488
    Research PubMed PMC3875705
    Phoslactomycin
    Phoslactomycin B1

    lyketide synthase domains

    The domains in the polyketide synthase type I:

    Biosynthesis pathway of phoslactomycin

    The PKS of phoslactomycin has one loading domain, 7 modules and 6 proteins that encode PnA, PnB, PnC, PnD, PnE, and PnF. The biosynthesis starts the loading with the cyclohexyl- CoA. Stepping in each module, there always need the keto synthase (KS) to create the new linkage of carbon-carbon to elongate the chain, the acyl transferase to transfer acyl to ACP domain. Then ACP serves as the acyl carrier protein to the further reaction, and each module has the keto reductase at the end to reduce the ketone to hydroxyl group with more stable. Module 1 uses the precursor malonyl-CoA and dehydrase domain to create the double bond.

    Similarly, module 2, module 5, and module 7 have the same 5 domains KS-AT-ACP-DH-KR, but module 7 has one more domain at the end is thioesterase (TE) to create the ring member of the phoslactomycin product. Module 4 and module 6 have 4 domains which are KS-AT-ACP-KR and use the precursor ethylmalonyl-CoA. The final product is phoslactomycin.

    The biosynthesis of phoslactomycin. Type I polyketide pathway


    Cyclization to form phoslactomycin at TE domain

    Phoslactomycin family

    Isolation from Streptomyces platensis, PLM is produces. Genes PnT1 and PnT2 regulate the post-synthesis of PLM to form PLM B by the phosphorylation and added the amine group . Figure 4 is based on the biosynthesis analysis on the Gene journal introduced that PLM B is used to produce PLM A, and 4 more PLMs C-F. The PLM A-F are the post synthesis product of the biosynthesis of PLM with the modification of many enzyme PnT1-T8.

    The post synthesis of PLM biosynthesis to form PLM B and the other PLMs

    PLMs regulates the actin cytoskeleton as they induce actin depolymerization by the indirect way. In the experiment, PLM F does not affect to the polymerization of purified actin in vitro. However, PLM F enhances the phosphorylation of intracellular vimentin.


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