Apratoxin A

The Apratoxin biosynthetic pathway is an organization of type I modular mixed polyketide synthase/non-ribosomal peptide synthase (PKS/NRPS).

Genetically, the 58kb biosynthetic gene cluster is composed of 12 open reading frames (ORFs), as shown in Figure 1.

Each type I polyketide-synthase module consist of several domains with defined function, separated by short spacer regions.

The following Domains are proposed for the Apratoxin A biosynthesis: The growing chain, shown in Figure 1, is handed over from one thiol group to the next by trans-acylation and is released at the end by a cyclization, promoted by a cyclase enzyme.

Another acetyl-SCoA extension takes place and ACP transfers the polyketide portion to be modified at the beta-hydroxyl position, relevant to the thioester, to a methyl-carboxylic acid.

[2][3][4][5] Also, Apratoxin A has lacks the necessary selectivity to be a potential anti-tumor agent even though numerous reports have shown differential cytotoxicity in 60 tumor cell lines.

Figure 1, Proposed Biosynthesis of Apratoxin A. [ 2 ]