Biosynthetic studies of the DSP toxin DTX-4 and an okadaic acid diol ester

Abstract

Stable isotope incorporation experiments with I3C-and 180-labelled precursors show that all the carbon atoms in DTX-4 2 and an okadaic acid diol ester 3 are derived from acetate and glycolate, and also identify the acetate and glycolate derived oxygen atoms.

The Biosynthesis of Polyketide Metabolites by Dinoflagellates

“…5) (Macpherson et al, 2003). Incorporation patterns of the OA portion of these two analogs were revealed to be identical to DTX-4 (Needham et al, 1995;Wright et al, 1996). DTX-5a and -5b have very similar side chains, the only difference being the number of carbons in the diol portion of the ester side chain.…”

“…Carbons 1 and 2 remained unlabeled by either [1-13 C], [2-13 C]. This and the presence of vicinal hydroxyls at C1 and C2 suggest that the starter unit for this polyketide may be glycolic acid, which is also the starter unit for OA and the ester portion of DTX-4 (Needham et al, 1994(Needham et al, , 1995. Although amphidinols 2 and 4 share an identical carbon backbone, their acetate incorporation patterns were not the same.…”

“…However, DTX-5a has one fewer carbon in this region. Earlier experiments with DTX-4 indicated that this polyketide was constructed of contiguous acetate units and no C1 deletions were observed (Needham et al, 1995;Wright et al, 1996). Further, the ester portion of this side chain was introduced by the Baeyer-Villiger oxidation of a continuous polyketide chain.…”

Chemical Defenses: From Compounds to Communities

“…Interestingly, most of the intracellular toxin in P. lima is in the form of the hydrophilic molecule DTX-4, which the results of metabolic labeling studies have suggested to be a biosynthetic precursor of OA (Needham et al, 1995; (Fig. 1).…”

Studies of the Biosynthesis of DTX-5a and DTX-5b by the Dinoflagellate Prorocentrum maculosum: Regiospecificity of the Putative Baeyer−Villigerase and Insertion of a Single Amino Acid in a Polyketide Chain

“…12 These sulfated esters are essentially inactive toward PP1 and PP2A in vitro, and it has been proposed that the sulfated diesters are the initial biosynthetic products of the dinoflagellate. 13 The unique chemical structure and bioactivity of the DSP toxins have prompted extensive biosynthetic studies that have revealed much complexity. Initially it was observed that the toxins and two okadaic acid diol esters are labeled extensively from acetate in an unexpected pattern and some positions did not appear to be labeled.…”