Marinone is an antibiotic made by marine actinomycetes.
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 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.
External links
