Elucidating the structures of powerful fish toxins from algal blooms.

[NNadir]

3. I collected a few of the references in the paper relevant to biosynthesis...

...of polyketides.

The mechanism for brevotoxin that you showed from the Wikipedia reference to Brevetoxin via epoxidation would seem to make sense, especially owing to the susceptibility of epoxides to stereocontrol, as demonstrated in the lab by Sharpless and leading to his Nobel Prize.

The unsaturated acid would of course, be available, from acetate.

¹³C labeling experiments seem to demonstrate that in fact most of the carbons in the related fused ring system of yessotoxin are, in fact, derived from acetate. Yessotoxin, also a dinoflagellate product has more methyl functionalities than prymnesin, 10 to be precise, all of which originate in acetate except for one that is apparently derived from a methionine methyl group in the mechanism that sometimes allows for branching.

Tetrahedron 67 (2011) 877-880

There's a very nice review article on the subject of biosynthetic pathways for these "ladder ether" systems: Nat. Prod. Rep., 2014,31, 1101-1137

I've only gone far enough into these papers to say I've been there, which involves looking at the pictures and reading through a little bit - excerpts - of the text. If you don't have immediate access to the papers, PM me and I'll be happy to send you copies of the papers.

Support for the chain epoxide ring opening cascade is found from the fact that ¹⁸O labeling experiments show that the internal oxygens in these systems do not for the most part derive from acetate. It appears that they are from oxygen gas.

This is interesting in the sense that one of the effects of algal blooms is, of course, oxygen depletion of the water. However, the mechanism by which this oxygen depletion takes place involved the decay of dead organisms decaying during oxidation by aerobic organisms in the regions below the blooms. There is localized oxygen from photosynthesis probably in the live bloom itself.

It's interesting that relatively simple mechanisms can lead to such complexity. These are interesting organisms that we've been promoting in our unyielding efforts to kill the planet while we wait tirelessly for the grand renewable energy nirvana that never arrives.