Biosynthesis of the neurotoxin domoic acid in a bloom-forming diatom

Brunson, John K.; McKinnie, Shaun M. K.; Chekan, Jonathan R.; McCrow, John P.; Miles, Zachary D.; Bertrand, Erin M.; Bielinski, Vincent A.; Luhavaya, Hanna; Oborník, Miroslav; Smith, G. Jason; Hutchins, David A.; Allen, Andrew E.; Moore, Bradley S.

doi:10.1126/science.aau0382

Title: Biosynthesis of the neurotoxin domoic acid in a bloom-forming diatom

Journal Article · 26 September 2018 · Science

DOI: https://doi.org/10.1126/science.aau0382 · OSTI ID:1475479

;

; McCrow, John P.; Miles, Zachary D.;

;

; Luhavaya, Hanna; Oborník, Miroslav;

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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.

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Sponsoring Organization:: USDOE

Grant/Contract Number:: SC0008593

OSTI ID:: 1475479

Journal Information:: Science, Journal Name: Science Journal Issue: 6409 Vol. 361; ISSN 0036-8075

Publisher:: American Association for the Advancement of Science (AAAS)Copyright Statement

Country of Publication:: United States

Language:: English

References (59)

Biosynthesis of domoic acid by the diatomPseudo-nitzschia multiseries Ramsey, Una P.; Douglas, Donald J.; Walter, John A. Natural Toxins, Vol. 6, Issue 3-4 https://doi.org/10.1002/(SICI)1522-7189(199805/08)6:3/4<137::AID-NT28>3.0.CO;2-L	journal	May 1998
Rapid and reliable protein extraction from yeast Kushnirov, Vitaly V. Yeast, Vol. 16, Issue 9 https://doi.org/10.1002/1097-0061(20000630)16:9<857::AID-YEA561>3.0.CO;2-B	journal	January 2000
An unprecedented coastwide toxic algal bloom linked to anomalous ocean conditions McCabe, Ryan M.; Hickey, Barbara M.; Kudela, Raphael M. Geophysical Research Letters, Vol. 43, Issue 19 https://doi.org/10.1002/2016GL070023	journal	October 2016
Expression and Detection of Inducible Nitric Oxide Synthase in Experimental Models of Inflammation Luss, Hartmut; Nussler, Natascha C.; Beger, Hans-G. Methods, Vol. 10, Issue 1 https://doi.org/10.1006/meth.1996.0078	journal	August 1996
Domoic acid: A dementia-inducing excitotoxic food poison with kainic acid receptor specificity Stewart, Gregory R.; Zorumski, Charles F.; Price, Madelon T. Experimental Neurology, Vol. 110, Issue 1 https://doi.org/10.1016/0014-4886(90)90057-Y	journal	October 1990
Isolation and structure of aromelic acid A and B. New kainoids of Konno, Katsuhiro; Shirahama, Haruhisa; Matsumoto, Takeshi Tetrahedron Letters, Vol. 24, Issue 9 https://doi.org/10.1016/S0040-4039(00)81571-3	journal	January 1983
Neurotoxin domoic acid produces cytotoxicity via kainate- and ampa-sensitive receptors in cultured cortical neurones Larm, J. A.; Beart, P. M.; Cheung, N. S. Neurochemistry International, Vol. 31, Issue 5 https://doi.org/10.1016/S0197-0186(97)00030-2	journal	November 1997
Trends in the surface chlorophyll of the California Current: Merging data from multiple ocean color satellites Kahru, Mati; Kudela, Raphael M.; Manzano-Sarabia, Marlenne Deep Sea Research Part II: Topical Studies in Oceanography, Vol. 77-80 https://doi.org/10.1016/j.dsr2.2012.04.007	journal	November 2012
Harmful algal blooms and climate change: Learning from the past and present to forecast the future Wells, Mark L.; Trainer, Vera L.; Smayda, Theodore J. Harmful Algae, Vol. 49 https://doi.org/10.1016/j.hal.2015.07.009	journal	November 2015
Chronic low-level exposure to the common seafood toxin domoic acid causes cognitive deficits in mice Lefebvre, Kathi A.; Kendrick, Preston S.; Ladiges, Warren Harmful Algae, Vol. 64 https://doi.org/10.1016/j.hal.2017.03.003	journal	April 2017
Improved Prediction of Signal Peptides: SignalP 3.0 Dyrløv Bendtsen, Jannick; Nielsen, Henrik; von Heijne, Gunnar Journal of Molecular Biology, Vol. 340, Issue 4, p. 783-795 https://doi.org/10.1016/j.jmb.2004.05.028	journal	July 2004
High-throughput production of human proteins for crystallization: The SGC experience Savitsky, Pavel; Bray, James; Cooper, Christopher D. O. Journal of Structural Biology, Vol. 172, Issue 1 https://doi.org/10.1016/j.jsb.2010.06.008	journal	October 2010
Chemistry of domoic acid, isodomoic acids, and their analogues Clayden, Jonathan; Read, Benjamin; Hebditch, Katherine R. Tetrahedron, Vol. 61, Issue 24 https://doi.org/10.1016/j.tet.2005.04.003	journal	June 2005
Practical synthesis of 1,5-dimethyl substituted conjugated polyenes from geranyl acetate Zhao, Yu-Jun; Loh, Teck-Peng Tetrahedron, Vol. 64, Issue 22 https://doi.org/10.1016/j.tet.2008.03.094	journal	May 2008
Condensation of the isoprenoid and amino precursors in the biosynthesis of domoic acid Savage, Thomas J.; Smith, G. Jason; Clark, Amy T. Toxicon, Vol. 59, Issue 1 https://doi.org/10.1016/j.toxicon.2011.10.010	journal	January 2012
Phylogenetic analyses of transcriptome data resolve familial assignments for genera of the red-algal Acrochaetiales-Palmariales Complex (Nemaliophycidae) Saunders, Gary W.; Jackson, Chris; Salomaki, Eric D. Molecular Phylogenetics and Evolution, Vol. 119 https://doi.org/10.1016/j.ympev.2017.11.002	journal	February 2018
Oxidative Cyclization in Natural Product Biosynthesis Tang, Man-Cheng; Zou, Yi; Watanabe, Kenji Chemical Reviews, Vol. 117, Issue 8 https://doi.org/10.1021/acs.chemrev.6b00478	journal	December 2016
Two Distinct Mechanisms for C–C Desaturation by Iron(II)- and 2-(Oxo)glutarate-Dependent Oxygenases: Importance of α-Heteroatom Assistance Dunham, Noah P.; Chang, Wei-chen; Mitchell, Andrew J. Journal of the American Chemical Society, Vol. 140, Issue 23 https://doi.org/10.1021/jacs.8b01933	journal	April 2018
Farnesyl Diphosphate Analogues with ω-Bioorthogonal Azide and Alkyne Functional Groups for Protein Farnesyl Transferase-Catalyzed Ligation Reactions Labadie, Guillermo R.; Viswanathan, Rajesh; Poulter, C. Dale The Journal of Organic Chemistry, Vol. 72, Issue 24 https://doi.org/10.1021/jo7017747	journal	November 2007
Biosynthesis of Iridoid Glucosides in Patrinia gibbosa Xie, Shan; Uesato, Shinichi; Fujita, Tetsuro Journal of Natural Products, Vol. 52, Issue 4 https://doi.org/10.1021/np50064a005	journal	July 1989
Efficient Total Synthesis of Lycophyll (ψ,ψ-Carotene-16,16‘-diol) Jackson, Henry L.; Nadolski, Geoffry T.; Braun, Cristi Organic Process Research & Development, Vol. 9, Issue 6 https://doi.org/10.1021/op050137f	journal	November 2005
Structure of Kainic Acid and its Isomer, Allokainic Acid Nitta, I.; Watase, H.; Tomiie, Y. Nature, Vol. 181, Issue 4611 https://doi.org/10.1038/181761b0	journal	March 1958
Host-specific adaptation governs the interaction of the marine diatom, Pseudo-nitzschia and their microbiota Sison-Mangus, Marilou P.; Jiang, Sunny; Tran, Kevin N. The ISME Journal, Vol. 8, Issue 1 https://doi.org/10.1038/ismej.2013.138	journal	August 2013
The Phaeodactylum genome reveals the evolutionary history of diatom genomes Bowler, Chris; Allen, Andrew E.; Badger, Jonathan H. Nature, Vol. 456, Issue 7219 https://doi.org/10.1038/nature07410	journal	October 2008
Minimum Information about a Biosynthetic Gene cluster Medema, Marnix H.; Kottmann, Renzo; Yilmaz, Pelin Nature Chemical Biology, Vol. 11, Issue 9 https://doi.org/10.1038/nchembio.1890	journal	August 2015
Enzymatic assembly of DNA molecules up to several hundred kilobases Gibson, Daniel G.; Young, Lei; Chuang, Ray-Yuan Nature Methods, Vol. 6, Issue 5, p. 343-345 https://doi.org/10.1038/nmeth.1318	journal	April 2009
The Phyre2 web portal for protein modeling, prediction and analysis Kelley, Lawrence A.; Mezulis, Stefans; Yates, Christopher M. Nature Protocols, Vol. 10, Issue 6 https://doi.org/10.1038/nprot.2015.053	journal	May 2015
Six domoic acid related compounds from the red alga, Chondria armata, and domoic acid biosynthesis by the diatom, Pseudo-nitzschia multiseries Maeno, Yukari; Kotaki, Yuichi; Terada, Ryuta Scientific Reports, Vol. 8, Issue 1 https://doi.org/10.1038/s41598-017-18651-w	journal	January 2018
Expansion of chemical space for natural products by uncommon P450 reactions Zhang, Xingwang; Li, Shengying Natural Product Reports, Vol. 34, Issue 9 https://doi.org/10.1039/C7NP00028F	journal	January 2017
Whole-cell response of the pennate diatom Phaeodactylum tricornutum to iron starvation Allen, A. E.; LaRoche, J.; Maheswari, U. Proceedings of the National Academy of Sciences, Vol. 105, Issue 30 https://doi.org/10.1073/pnas.0711370105	journal	July 2008
Phytoplankton–bacterial interactions mediate micronutrient colimitation at the coastal Antarctic sea ice edge Bertrand, Erin M.; McCrow, John P.; Moustafa, Ahmed Proceedings of the National Academy of Sciences, Vol. 112, Issue 32 https://doi.org/10.1073/pnas.1501615112	journal	July 2015
Climatic regulation of the neurotoxin domoic acid McKibben, S. Morgaine; Peterson, William; Wood, A. Michelle Proceedings of the National Academy of Sciences, Vol. 114, Issue 2 https://doi.org/10.1073/pnas.1606798114	journal	January 2017
Ocean warming since 1982 has expanded the niche of toxic algal blooms in the North Atlantic and North Pacific oceans Gobler, Christopher J.; Doherty, Owen M.; Hattenrath-Lehmann, Theresa K. Proceedings of the National Academy of Sciences, Vol. 114, Issue 19 https://doi.org/10.1073/pnas.1619575114	journal	April 2017
PhyloBayes 3: a Bayesian software package for phylogenetic reconstruction and molecular dating Lartillot, Nicolas; Lepage, Thomas; Blanquart, Samuel Bioinformatics, Vol. 25, Issue 17 https://doi.org/10.1093/bioinformatics/btp368	journal	June 2009
edgeR: a Bioconductor package for differential expression analysis of digital gene expression data Robinson, M. D.; McCarthy, D. J.; Smyth, G. K. Bioinformatics, Vol. 26, Issue 1 https://doi.org/10.1093/bioinformatics/btp616	journal	November 2009
Identification and removal of ribosomal RNA sequences from metatranscriptomes Schmieder, Robert; Lim, Yan Wei; Edwards, Robert Bioinformatics, Vol. 28, Issue 3 https://doi.org/10.1093/bioinformatics/btr669	journal	December 2011
featureCounts: an efficient general purpose program for assigning sequence reads to genomic features Liao, Y.; Smyth, G. K.; Shi, W. Bioinformatics, Vol. 30, Issue 7 https://doi.org/10.1093/bioinformatics/btt656	journal	November 2013
SeaView Version 4: A Multiplatform Graphical User Interface for Sequence Alignment and Phylogenetic Tree Building Gouy, M.; Guindon, S.; Gascuel, O. Molecular Biology and Evolution, Vol. 27, Issue 2 https://doi.org/10.1093/molbev/msp259	journal	October 2009
Ultrafast Approximation for Phylogenetic Bootstrap Minh, B. Q.; Nguyen, M. A. T.; von Haeseler, A. Molecular Biology and Evolution, Vol. 30, Issue 5 https://doi.org/10.1093/molbev/mst024	journal	February 2013
IQ-TREE: A Fast and Effective Stochastic Algorithm for Estimating Maximum-Likelihood Phylogenies Nguyen, Lam-Tung; Schmidt, Heiko A.; von Haeseler, Arndt Molecular Biology and Evolution, Vol. 32, Issue 1 https://doi.org/10.1093/molbev/msu300	journal	November 2014
Assessment of aryl hydrocarbon receptor complex interactions using pBEVY plasmids: expressionvectors with bi-directional promoters for use in Saccharomyces cerevisiae Miller, C. Nucleic Acids Research, Vol. 26, Issue 15 https://doi.org/10.1093/nar/26.15.3577	journal	August 1998
FragGeneScan: predicting genes in short and error-prone reads Rho, Mina; Tang, Haixu; Ye, Yuzhen Nucleic Acids Research, Vol. 38, Issue 20 https://doi.org/10.1093/nar/gkq747	journal	August 2010
HMMER web server: interactive sequence similarity searching Finn, R. D.; Clements, J.; Eddy, S. R. Nucleic Acids Research, Vol. 39, Issue suppl https://doi.org/10.1093/nar/gkr367	journal	May 2011
InterPro in 2017—beyond protein family and domain annotations Finn, Robert D.; Attwood, Teresa K.; Babbitt, Patricia C. Nucleic Acids Research, Vol. 45, Issue D1 https://doi.org/10.1093/nar/gkw1107	journal	November 2016
Finding a partner in the ocean: molecular and evolutionary bases of the response to sexual cues in a planktonic diatom Basu, Swaraj; Patil, Shrikant; Mapleson, Daniel New Phytologist, Vol. 215, Issue 1 https://doi.org/10.1111/nph.14557	journal	April 2017
Plastid proteome prediction for diatoms and other algae with secondary plastids of the red lineage Gruber, Ansgar; Rocap, Gabrielle; Kroth, Peter G. The Plant Journal, Vol. 81, Issue 3 https://doi.org/10.1111/tpj.12734	journal	January 2015
The Genome of the Diatom Thalassiosira Pseudonana: Ecology, Evolution, and Metabolism Armbrust, E. V. Science, Vol. 306, Issue 5693 https://doi.org/10.1126/science.1101156	journal	October 2004
Algal toxin impairs sea lion memory and hippocampal connectivity, with implications for strandings Cook, P. F.; Reichmuth, C.; Rouse, A. A. Science, Vol. 350, Issue 6267 https://doi.org/10.1126/science.aac5675	journal	December 2015
Sodium borohydride: A versatile reagent in the reductive N -monoalkylation of α-amino acids and α-amino methyl esters Verardo, Giancarlo; Geatti, Paola; Pol, Elena Canadian Journal of Chemistry, Vol. 80, Issue 7 https://doi.org/10.1139/v02-083	journal	July 2002
Chemistry of the shellfish toxin domoic acid: characterization of related compounds Walter, John A.; Falk, Michael; Wright, Jeffrey L. C. Canadian Journal of Chemistry, Vol. 72, Issue 2 https://doi.org/10.1139/v94-064	journal	February 1994
Data access for the 1,000 Plants (1KP) project Matasci, Naim; Hung, Ling-Hong; Yan, Zhixiang GigaScience, Vol. 3, Issue 1 https://doi.org/10.1186/2047-217X-3-17	journal	October 2014
The Marine Microbial Eukaryote Transcriptome Sequencing Project (MMETSP): Illuminating the Functional Diversity of Eukaryotic Life in the Oceans through Transcriptome Sequencing Keeling, Patrick J.; Burki, Fabien; Wilcox, Heather M. PLoS Biology, Vol. 12, Issue 6 https://doi.org/10.1371/journal.pbio.1001889	journal	June 2014
Genome-Wide Transcriptome Analyses of Silicon Metabolism in Phaeodactylum tricornutum Reveal the Multilevel Regulation of Silicic Acid Transporters Sapriel, Guillaume; Quinet, Michelle; Heijde, Marc PLoS ONE, Vol. 4, Issue 10 https://doi.org/10.1371/journal.pone.0007458	journal	October 2009
Characterization of Renal Toxicity in Mice Administered the Marine Biotoxin Domoic Acid Funk, Jason A.; Janech, Michael G.; Dillon, Joshua C. Journal of the American Society of Nephrology, Vol. 25, Issue 6 https://doi.org/10.1681/ASN.2013080836	journal	February 2014
Pseudo-nitzschia (Bacillariophyceae) species, domoic acid and amnesic shellfish poisoning: revisiting previous paradigms Lelong, Aurélie; Hégaret, Hélène; Soudant, Philippe Phycologia, Vol. 51, Issue 2 https://doi.org/10.2216/11-37.1	journal	March 2012
Refinement of the Diatom Episome Maintenance Sequence and Improvement of Conjugation-Based DNA Delivery Methods Diner, Rachel E.; Bielinski, Vincent A.; Dupont, Christopher L. Frontiers in Bioengineering and Biotechnology, Vol. 4 https://doi.org/10.3389/fbioe.2016.00065	journal	August 2016
In Utero Domoic Acid Toxicity: A Fetal Basis to Adult Disease in the California Sea Lion (Zalophus californianus) Ramsdell, John; Zabka, Tanja Marine Drugs, Vol. 6, Issue 2 https://doi.org/10.3390/md6020262	journal	June 2008
Repeated Dietary Exposure to Low Levels of Domoic Acid and Problems with Everyday Memory: Research to Public Health Outreach Grattan, Lynn; Boushey, Carol; Liang, Yuanyuan Toxins, Vol. 10, Issue 3 https://doi.org/10.3390/toxins10030103	journal	February 2018
Effects of changing p CO ₂ and phosphate availability on domoic acid production and physiology of the marine harmful bloom diatom Pseudo-nitzschia multiseries Sun, Jun; Hutchins, David A.; Feng, Yuanyuan Limnology and Oceanography, Vol. 56, Issue 3 https://doi.org/10.4319/lo.2011.56.3.0829	journal	March 2011

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