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

Abstract

The biosynthetic origins of the diarrhetic shellfish poisoning toxins DTX-5a and DTX-5b have been elucidated by supplementing cultures of the producing organism Prorocentrum maculosum with stable isotope labeled precursors and determining the incorporation patterns by 13 C NMR spectroscopy. The amino acid residue in the sulfated side chain is found to originate from glycine, and oxygen insertion in the chain is shown to occur after polyketide formation.

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).…”

The Mechanism of Diarrhetic Shellfish Poisoning Toxin Production in Prorocentrum spp.: Physiological and Molecular Perspectives

“…Several precursor incorporation studies have also indicated that the PKS pathway participates in DSP toxin biosynthesis [137,138,139,140,141]. Glycolate from photorespiration is a deemed precursor of OA synthesis and side chains of DTX-5 (side chain c and d of R 5 in Figure 1).…”

“…Glycolate from photorespiration is a deemed precursor of OA synthesis and side chains of DTX-5 (side chain c and d of R 5 in Figure 1). They are formed through the typical polyketide process, the consecutive addition of acetate and interruption by Favorskii-like rearrangement [138]. The side chains of DTX-5 ligate OA through an ester bond between glycolate-derived hydroxyl group and terminal carboxyl group of OA [140].…”

“…In addition, amide in the side chain of DTXs may be replaced by glycine. After the incorporation of amino acids as precursors, chain termination or the midchain extension of units is usually directed by hybrid NRPS/PKS in cyanobacteria [136,142] and actinomycetes [142], suggesting that OA and DTXs are generated by hybrid NRPS/PKS [138]. …”

Six-Membered Ring Spiranes: Carbocycles and Heterocycles with Oxygen

“…Consequently, a large variety of methods have been used to synthesize this class of compounds [85]. The latest papers concerning the synthesis of 1,7-dioxaspiro [5.5]undecane subunits reported eventually improvements of the already reviewed spiroketalizations [86][87][88][89].…”