Codinaeopsin is an antimalarial isolated from a fungal

Fungus

A fungus is a member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds , as well as the more familiar mushrooms. These organisms are classified as a kingdom, Fungi, which is separate from plants, animals, and bacteria...

 isolate found in white yemeri trees (Vochysia guatemalensis) in Costa Rica

Costa Rica

Costa Rica , officially the Republic of Costa Rica is a multilingual, multiethnic and multicultural country in Central America, bordered by Nicaragua to the north, Panama to the southeast, the Pacific Ocean to the west and the Caribbean Sea to the east....

. It is reported to have bioactivity against Plasmodium falciparum

Plasmodium falciparum

Plasmodium falciparum is a protozoan parasite, one of the species of Plasmodium that cause malaria in humans. It is transmitted by the female Anopheles mosquito. Malaria caused by this species is the most dangerous form of malaria, with the highest rates of complications and mortality...

with an IC₅₀ = 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

Biosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...

 of codinaeopsin is manufactured by a polyketide synthase

Polyketide synthase

Polyketide synthases are a family of multi-domain enzymes or enzyme complexes that produce polyketides, a large class of secondary metabolites, in bacteria, fungi, plants, and a few animal lineages...

- nonribosomal peptide synthetase (PKS-NRPS) hybrid.

Formation of linear polyketide

The first step of the biosynthesis of codinaeopsin involves the assembly of the a linear polyketide

Polyketide

Polyketides are secondary metabolites from bacteria, fungi, plants, and animals. Polyketides are usually biosynthesized through the decarboxylative condensation of malonyl-CoA derived extender units in a similar process to fatty acid synthesis...

 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-pyrrolidindione)

L-Tryptophan

Tryptophan

Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...

 is introduced by a nonribosomal peptide synthetase (NRPS) module and results in the central heterocyclic tetramic acid (2,4-pyrrolidindione). The formal oxidation-reduction is found to be achieved by a series of tautomeric shifts involving enol

Enol

Enols are alkenes with a hydroxyl group affixed to one of the carbon atoms composing the double bond. Alkenes with a hydroxyl group on both sides of the double bond are called enediols. Deprotonated anions of enols are called enolates...

 and imine

Imine

An imine is a functional group or chemical compound containing a carbon–nitrogen double bond, with the nitrogen attached to a hydrogen atom or an organic group. If this group is not a hydrogen atom, then the compound is known as a Schiff base...

 intermediates in the ring and consistent by discovery both C-2’ epimer

Epimer

In chemistry, epimers are diastereomers that differ in configuration of only one stereogenic center. Diastereomers are a class of stereoisomers that are non-superposable, non-mirror images of one another....

s.

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

Lovastatin

Lovastatin is a member of the drug class of statins, used for lowering cholesterol in those with hypercholesterolemia and so preventing cardiovascular disease...

and solanapyrone.