Oceanic harmful algal blooms of Pseudo-nitzschia diatoms produce the potent mammalian neurotoxin domoic acid (DA). Despite decades of research, the molecular basis for its biosynthesis is not known. By using growth conditions known to induce DA production in Pseudo-nitzschia multiseries, we implemented transcriptome sequencing in order to identify DA biosynthesis genes that colocalize in a genomic four-gene cluster. We biochemically investigated the recombinant DA biosynthetic enzymes and linked their mechanisms to the construction of DA's diagnostic pyrrolidine skeleton, establishing a model for DA biosynthesis. Knowledge of the genetic basis for toxin production provides an orthogonal approach to bloom monitoring and enables study of environmental factors that drive oceanic DA production.

Center for Marine Biotechnology and Biomedicine Scripps Institution of Oceanography University of California San Diego La Jolla CA 92093 USA

Department of Biology Dalhousie University Halifax Nova Scotia B3H 4R2 Canada

Institute of Parasitology University of South Bohemia and Biology Center CAS Branišovská 31 370 05 České Budějovice Czech Republic

Integrative Oceanography Division Scripps Institution of Oceanography University of California San Diego La Jolla CA 92037 USA

Marine and Environmental Biology Department of Biological Sciences University of Southern California Los Angeles CA 90089 USA

Microbial and Environmental Genomics Group J Craig Venter Institute La Jolla CA 92037 USA

Moss Landing Marine Laboratories 8272 Moss Landing Road Moss Landing CA 95039 USA

Skaggs School of Pharmacy and Pharmaceutical Sciences University of California San Diego La Jolla CA 92093 USA

Synthetic Biology and Bioenergy Group J Craig Venter Institute La Jolla CA 92037 USA

Science. 2018 Sep 28;361(6409):1308-1309. doi: 10.1126/science.aau9067. PubMed

Nat Chem Biol. 2018 Dec;14(12):1067. doi: 10.1038/s41589-018-0175-4. PubMed

Zobrazit více v PubMed

Wells ML et al., Harmful Algae 49, 68–93 (2015). PubMed PMC

McKibben SM et al., Proc. Natl. Acad. Sci. U.S.A. 114, 239–244 (2017). PubMed PMC

Gobler CJ et al., Proc. Natl. Acad. Sci. U.S.A. 114, 4975–4980 (2017). PubMed PMC

McCabe RM et al., Geophys. Res. Lett 43, 10366–10376 (2016). PubMed PMC

Stewart GR, Zorumski CF, Price MT, Olney JW, Exp. Neurol 110, 127–138 (1990). PubMed

Larm JA, Beart PM, Cheung NS, Neurochem. Int 31, 677–682 (1997). PubMed

Funk JA et al., J. Am. Soc. Nephrol 25, 1187–1197 (2014). PubMed PMC

Lefebvre KA et al., Harmful Algae 64, 20–29 (2017). PubMed PMC

Ramsdell JS, Zabka TS, Mar. Drugs 6, 262–290 (2008). PubMed PMC

Grattan LM et al., Toxins (Basel) 10, 103 (2018). PubMed PMC

Cook PF et al., Science 350, 1545–1547 (2015). PubMed

Lelong A, Hégaret H, Soudant P, Bates SS, Phycologia 51, 168–216 (2012).

Sison-Mangus MP, Jiang S, Tran KN, Kudela RM, ISME J 8, 63–76 (2014). PubMed PMC

Ramsey UP, Douglas DJ, Walter JA, Wright JL, Nat. Toxins 6, 137–146 (1998). PubMed

Savage TJ, Smith GJ, Clark AT, Saucedo PN, Toxicon 59, 25–33 (2012). PubMed

Zhang X, Li S, Nat. Prod. Rep 34, 1061–1089 (2017). PubMed

Sun J et al., Limnol. Oceanogr 56, 829–840 (2011).

Medema MH et al., Nat. Chem. Biol 11, 625–631 (2015). PubMed PMC

Armbrust EV et al., Science 306, 79–86 (2004). PubMed

Bowler C et al., Nature 456, 239–244 (2008). PubMed

Allen AE et al., Proc. Natl. Acad. Sci. U.S.A. 105, 10438–10443 (2008). PubMed PMC

Sapriel G et al., PLOS ONE 4, e7458 (2009). PubMed PMC

Kelley LA, Mezulis S, Yates CM, Wass MN,Sternberg MJE, Nat. Protoc 10, 845–858 (2015). PubMed PMC

Maeno Y et al., Sci. Rep 8, 356 (2018). PubMed PMC

Clayden J, Read B, Hebditch KR, Tetrahedron 61, 5713–5724 (2005).

Nitta I, Watase H, Tomiie Y, Nature 181, 761–762 (1958). PubMed

Konno K, Shirahama H, Matsumoto T, Tetrahedron Lett. 24, 939–942 (1983).

Saunders GW, Jackson C, Salomaki ED, Mol. Phylogenet. Evol 119, 151–159 (2018). PubMed

Matasci N et al., Gigascience 3, 17 (2014). PubMed PMC

Basu S et al., New Phytol. 215, 140–156 (2017). PubMed PMC

Keeling PJ et al., PLOS Biol. 12, e1001889 (2014). PubMed PMC

Proximity proteomics in a marine diatom reveals a putative cell surface-to-chloroplast iron trafficking pathway

Genetic tool development in marine protists: emerging model organisms for experimental cell biology

In the beginning was the word: How terminology drives our understanding of endosymbiotic organelles