Domoic acid biosynthesis in the red alga Chondria armata suggests a complex evolutionary history for toxin production

Abstract

Significance Originally isolated from the red alga Chondria armata , domoic acid (DA) is best known as a potent marine neurotoxin produced by oceanic harmful algal blooms of planktonic diatoms. Sequencing efforts to date of kainoid-producing red algae have focused exclusively on a closely related molecule, kainic acid, leaving a gap in the understanding of DA biosynthesis in red algae and its evolutionary linkage to diatoms. Here, we present the phylogenetic and biochemical investigation of DA biosynthesis in C. armata . This work demonstrates the high synteny of DA biosynthetic genes between relatively distant taxonomic groups of algae and suggests a complex evolutionary history for DA biosynthesis involving gene transfer and neofunctionalization.

Towards a Better Understanding of Toxin Biosynthesis in Seaweeds

“…Taken together, this enlightening work by Steele and colleagues clarifies for the first time the modalities of DA biosynthesis in red algae [5] . These discoveries first represent significant advances in the fields of chemical ecology and toxicology of marine natural products.…”

“…This work also provides interesting perspectives in metabolic engineering since it suggests that the co‐occurrence of a similar secondary metabolic pathway in phylogenetically distant marine organisms may guide further identification of uncharacterized biosynthetic routes of valuable marine drugs. Finally, this work reports unique data to better understand the evolution of toxic metabolite biosynthesis among algal species by suggesting how a combination of horizontal gene transfer events and enzyme neofunctionalization could lead to the production of neurotoxic compounds in phylogenetically distant marine species [3–5] …”

“…Yet, this missing piece is essential to assess the origin and evolution of kainoid production in micro‐ and macroalgae. Remarkably, key insights were recently provided by the groups of Chekan and Moore as results of a comprehensive study to specifically elucidate the biosynthetic pathway of DA in the red alga C. armata as well as its complex evolution among marine species [5] …”

Biosynthesis of Haloterpenoids in Red Algae via Microbial-like Type I Terpene Synthases

“…Eukaryotic biosynthetic gene clusters (BGCs) are typically spaced over several kilobases, have large intergenic regions, and are often flanked, or contain, viral retrotransposable elements . For example, in octocorals, TS genes were found to be physically colocalized with genes encoding putative terpenoid tailoring enzymes. , In red algae, there are a handful of examples of gene clustering; however, algal BGCs known to date either contain vanadium-dependent haloperoxidase (VHPO) or MTS encoding genes. , Previously identified MTS-containing gene clusters are associated with kainoid-producing red macroalgae, where the MTS catalyzes an N -prenylation reaction.…”

Algal Kainoid Synthases Exhibit Substrate-Dependent Hydroxylation and Cyclization Activities

“…Intriguingly, N-geranyl-(3R)-hydroxy-L-glutamic acid was isolated in microgram quantities from domoic acid-producing C. armata. 16 Comparison of the glutamate moiety 1 H and 13 C NMR chemical shifts between 3 and this red algal metabolite supported that the β-hydroxy group was installed at the pro-R hydrogen (Tables S1 and S2). 16 To unequivocally assign the stereochemistry of 3, 3R-hydroxy-L-glutamic acid was enantioselectively synthesized from L-malic acid 17,18 and then condensed with 7-carboxygeranial via reductive amination.…”