Codinaeopsin is an
antimalarial isolated from a
fungal isolate found in white yemeri trees (''Vochysia guatemalensis'') in
Costa Rica
Costa Rica (, ; ; literally "Rich Coast"), officially the Republic of Costa Rica ( es, República de Costa Rica), is a country in the Central American region of North America, bordered by Nicaragua to the north, the Caribbean Sea to the no ...
. It is reported to have bioactivity against ''
Plasmodium falciparum
''Plasmodium falciparum'' is a Unicellular organism, unicellular protozoan parasite of humans, and the deadliest species of ''Plasmodium'' that causes malaria in humans. The parasite is transmitted through the bite of a female ''Anopheles'' mosqu ...
'' with an IC
50 = 2.3 μg/mL (4.7 μM). Pure codinaeopsin was reported to be isolated with a total yield of 18 mg/mL from cultured fungus.
The
biosynthesis
Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. ...
of codinaeopsin involves a
polyketide synthase-
nonribosomal peptide synthetase (PKS-NRPS) hybrid.
Biosynthesis
Formation of linear polyketide
The first step of the biosynthesis of codinaeopsin involves the assembly of the a linear
polyketide by use of seven modules and incorporation of six
methylmalonyl CoAs and one
malonyl CoA by
polyketide synthases (type I PKSs).
[
]
Formation of tetramic acid (2,4-pyrrolidinone)
L-Tryptophan is introduced by a nonribosomal peptide synthetase (NRPS) module and results in the central heterocyclic tetramic acid (2,4-pyrrolidinone). The formal oxidation-reduction is found to be achieved by a series of tautomeric shifts involving enol and imine intermediates in the ring and consistent by discovery both C-2’ epimers.[
]
Cyclization of PKS-assembled unit
The PKS unit is hypothesized to cyclize by a Diels-Alder-like addition similar to other natural products such as lovastatin and solanapyrone.
References
{{reflist
Antimalarial agents