Synthesis and identification of proposed biosynthetic intermediates of saxitoxin in the cyanobacterium Anabaena circinalis (TA04) and the dinoflagellate Alexandrium tamarense (Axat-2)

Tsuchiya, Shigeki; Cho, Yuko; Konoki, Keiichi; Nagasawa, Kazuo; Oshima, Yasukatsu; Yotsu‐Yamashita, Mari

doi:10.1039/c4ob00071d

Cited by 53 publications

(72 citation statements)

References 32 publications

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“…[152]. Recently, genetically predicted biosynthetic intermediate of STX such as Int-A, Int-C2 and D2 have been identified and quantified in Anabaena circinalis [153], which support the biosynthetic route completely as proposed by Kellmann et al [149]. …”

Section: Saxitoxinsupporting

confidence: 53%

Impact of Environmental Factors on the Regulation of Cyanotoxin Production

Boopathi

2014

Toxins

138

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Cyanobacteria are capable of thriving in almost all environments. Recent changes in climatic conditions due to increased human activities favor the occurrence and severity of harmful cyanobacterial bloom all over the world. Knowledge of the regulation of cyanotoxins by the various environmental factors is essential for effective management of toxic cyanobacterial bloom. In recent years, progress in the field of molecular mechanisms involved in cyanotoxin production has paved the way for assessing the role of various factors on the cyanotoxin production. In this review, we present an overview of the influence of various environmental factors on the production of major group of cyanotoxins, including microcystins, nodularin, cylindrospermopsin, anatoxins and saxitoxins.

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Section: Saxitoxinsupporting

confidence: 53%

Impact of Environmental Factors on the Regulation of Cyanotoxin Production

Boopathi

2014

Toxins

138

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“…For example, the synthesis of 21 required a linear six-step sequence to access each ketone. 13 Thus, we anticipate the SxtA AONS has potential as a useful biocatalyst.…”

mentioning

confidence: 95%

Chemistry of a Unique Polyketide-like Synthase

et al. 2018

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Like many complex natural products, the intricate architecture of saxitoxin (STX) has hindered full exploration of this scaffold’s utility as a tool for studying voltage-gated sodium ion channels and as a pharmaceutical agent. Established chemical strategies can provide access to the natural product; however, a chemoenzymatic route to saxitoxin that could provide expedited access to related compounds has not been devised. The first step toward realizing a chemoenzymatic approach toward this class of molecules is the elucidation of the saxitoxin biosynthetic pathway. To date, a biochemical link between STX and its putative biosynthetic enzymes has not been demonstrated. Herein, we report the first biochemical characterization of any enzyme involved in STX biosynthesis. Specifically, the chemical functions of a polyketide-like synthase, SxtA, from the cyanobacteria Cylindrospermopsis raciborskii T3 are elucidated. This unique megasynthase is comprised of four domains: methyltransferase (MT), GCN5-related N-acetyl-transferase (GNAT), acyl carrier protein (ACP), and the first example of an 8-amino-7-oxononanoate synthase (AONS) associated with a multi-domain synthase. We have established that this single polypeptide carries out the formation of two carbon-carbon bonds, two decarboxylation events and a stereospecific protonation to afford the linear biosynthetic precursor to STX (4). The synthetic utility of the SxtA AONS is demonstrated by the synthesis of a suite of α-amino ketones from the corresponding α-amino acid in a single step.

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“…Specifically in the timing of sulfation events that convert saxitoxin into gonyautoxins [19] and the formation of the first proposed biosynthetic intermediate, 12. [20] Several hypotheses on the biosynthetic route towardP STs have been reported. [21] Gene clusters encoding enzymes involved in saxitoxin biosynthesis were first discovered by Neilan and co-workersi nCylindrospermopsis raciborskii.…”

Section: Saxitoxins and Gonyautoxinsmentioning

confidence: 99%

“…Using mass spectrometry analysisi nc ombination with synthetically generateds tandards, Yotsu-Yamashita and co-workers have identified several new potential biosynthetic intermediates, including 12 ( Figure 3), and the identification of 16 in dinoflagellate extracts ( Figure 3B,i nset). [20,29] Characterization of SxtA supports 12 as ab iosynthetic intermediate. [28a] However, in vitro reactions with sxt oxygenases suggestt hat decarbamoyl 11-a-hydroxysaxitoxin (16)i sn ot on the pathway to saxitoxin (3)a nd that it is more likely as hunt product of this biosynthetic pathway.…”

Section: Saxitoxins and Gonyautoxinsmentioning

confidence: 99%

Natural Voltage‐Gated Sodium Channel Ligands: Biosynthesis and Biology

Lukowski

Narayan

2019

ChemBioChem

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Natural product biosynthetic pathways are composed of enzymes that use powerful chemistry to assemble complex molecules. Small molecule neurotoxins are examples of natural products with intricate scaffolds which often have high affinities for their biological targets. The focus of this Minireview is small molecule neurotoxins targeting voltage‐gated sodium channels (VGSCs) and the state of knowledge on their associated biosynthetic pathways. There are three small molecule neurotoxin receptor sites on VGSCs associated with three different classes of molecules: guanidinium toxins, alkaloid toxins, and ladder polyethers. Each of these types of toxins have unique structural features which are assembled by biosynthetic enzymes and the extent of information known about these enzymes varies among each class. The biosynthetic enzymes involved in the formation of these toxins have the potential to become useful tools in the efficient synthesis of VGSC probes.

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Synthesis and identification of proposed biosynthetic intermediates of saxitoxin in the cyanobacterium Anabaena circinalis (TA04) and the dinoflagellate Alexandrium tamarense (Axat-2)

Cited by 53 publications

References 32 publications

Impact of Environmental Factors on the Regulation of Cyanotoxin Production

Impact of Environmental Factors on the Regulation of Cyanotoxin Production

Chemistry of a Unique Polyketide-like Synthase

Natural Voltage‐Gated Sodium Channel Ligands: Biosynthesis and Biology

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