Marinone
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Marinone is an
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...
made by marine
actinomycetes The Actinomycetales is an Scientific classification, order of Actinomycetota. A member of the order is often called an actinomycete. Actinomycetales are generally Gram-positive bacteria, gram-positive and anaerobic and have mycelia in a filamento ...
.


Biosynthesis

The proposed biosynthesis of marinone was first reported by Murray ''et al.'' in 2018. The biosynthesis of marinone begins with 1,3,6,8-tetrahydroxynaphthalene (THN), which is known to be biosynthesized via the condensation of five malonyl-coenzyme A units followed by the aromatization of the resulting pentaketide using a type III polyketide synthase. Next, THN undergoes geranylation or
farnesylation Prenylation (also known as isoprenylation or lipidation) is the addition of hydrophobic molecules to a protein or a biomolecule. It is usually assumed that prenyl groups (3-methylbut-2-en-1-yl) facilitate attachment to cell membranes, similar to ...
at the C-4 position, yielding 1 (Fig. 1). This transformation is catalyzed in vivo by NphB aromatic prenyltransferase in naphterpin biosynthesis or by CnqP3 or CnqP4 in marinone biosynthesis. Then, 1 undergoes oxidative dearomatization which is catalyzed by VCPO, which is a vanadium-dependent chloroperoxidase enzyme. This transformation yields compound 2. Compound 2 then undergoes two consecutive chlorinations at the C2 position, catalyzed by VCPO, to yield 4. Next, a VCPO catalyzed α-hydroxyketone rearrangement shifts the geranyl substituent from C-4 to C-3, yielding 5. Exposure of 5 to mildly basic conditions induces cyclization to yield the α-chloroepoxide, 6. This is followed by the reductive halogenation of the α-chloroepoxide to yield the hydroxynaphthoquinone, 7. Next, oxidation at the C-2 position and facile E/Z isomerization of the double bond affords the enone, 8, which undergoes a intramolecular hetero-Diels-Alder to yield debromomarinone. Lastly, the vanadium-dependent bromoperoxidase catalyzes the bromination of debromomarinone at the C-5 position to result in the formation of marinone.


References

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External links


Bioactive compounds from marine actinomycetes
Antibiotics Angucyclines Heterocyclic compounds with 4 rings Bromoarenes Oxygen heterocycles Terpeno-phenolic compounds