Fumitremorgins are tremorogenic metabolites of ''

Aspergillus ' () is a genus consisting of several hundred mold species found in various climates worldwide. ''Aspergillus'' was first catalogued in 1729 by the Italian priest and biologist Pier Antonio Micheli. Viewing the fungi under a microscope, Miche ...

'' and ''

Penicillium ''Penicillium'' () is a genus of Ascomycota, ascomycetous fungus, fungi that is part of the mycobiome of many species and is of major importance in the natural environment, in food spoilage, and in food and drug production. Some members of th ...

'' that belong to a class of naturally occurring 2,5-diketopiperazines.

Biosynthesis

Biosynthesis pathway of fumitremorgin pathway involves several different enzymes. FtmA is a

nonribosomal peptide Nonribosomal peptides (NRP) are a class of peptide secondary metabolites, usually produced by microorganisms like bacterium, bacteria and fungi. Nonribosomal peptides are also found in higher organisms, such as nudibranchs, but are thought to be ma ...

synthase. Both FtmB and FtmH are prenyltransferase. Three different

cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

monooxygenases involved in the biosynthesis of furmitremorgin C are FtmC, FtmE, and FtmG. Furthermore, FtmD is proposed to function as the

methyltransferase Methyltransferases are a large group of enzymes that all methylate their substrates but can be split into several subclasses based on their structural features. The most common class of methyltransferases is class I, all of which contain a Ro ...

. The synthesis starts with the formation of brevianamide F. FtmA catalyzes the nonribosomal peptide synthesis (NRPS) of this diketopiperazine product from two amino acids, L-tryptophan and

L-proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the Protein biosynthesis, biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine n ...

. Then, another enzyme, FtmB, prenylates the product to form tryprostatin B. At this point, there are two separate pathways. FtmE may cyclize tryprostatin B to form demethoxyfumitremorgin C, or FtmC may oxidize tryprostatin B to form desmethyltrprostatin A by adding a hydroxyl group to the C-6 of the

indole Indole is an organic compound with the formula . Indole is classified as an aromatic heterocycle. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered pyrrole ring. Indoles are derivatives of indole ...

ring. The later pathway is followed by methylation to form tryprostatin A. The enzyme that catalyzes this methylation reaction has not been fully identified, but FtmD is suspected to be the plausible candidate. Then, the cyclization of tryprostatin A produces fumitremorgin C by forming the C-N bond by FtmE. The subsequent hydroxylation of fumitremorgin C takes place at C-12 and C-13 to form 12α, 13α-dihydroxyfumitremorgin C by FtmG. Fumitremorgin B is formed by another prenyltransferase, FtmH, that prenylates at N-1 of the indole ring. : Proposed biosynthesis pathway

References

{{reflist Indole alkaloids Penicillium Diketopiperazines