- Title
- Heterologous expression of an unusual ketosynthase, SxtA, leads to production of saxitoxin intermediates in Escherichia coli
- Creator
- Soeriyadi, Angela H.; Mazmouz, Rabia; Pickford, Russell; Al-Sinawi, Bakir; Kellmann, Ralf; Pearson, Leanne A.; Neilan, Brett A.
- Relation
- ChemBioChem Vol. 22, Issue 5, p. 845-849
- Publisher Link
- http://dx.doi.org/10.1002/cbic.202000675
- Publisher
- Wiley
- Resource Type
- journal article
- Date
- 2021
- Description
- Paralytic shellfish toxins (PSTs) are neurotoxic alkaloids produced by freshwater cyanobacteria and marine dinoflagellates. Due to their antagonism of voltage-gated sodium channels in excitable cells, certain analogues are of significant pharmacological interest. The biosynthesis of the parent compound, saxitoxin, is initiated with the formation of 4-amino-3-oxo-guanidinoheptane (ethyl ketone) by an unusual polyketide synthase-like enzyme, SxtA. We have heterologously expressed SxtA from Raphidiopsis raciborskii T3 in Escherichia coli and analysed its activity in vivo. Ethyl ketone and a truncated analogue, methyl ketone, were detected by HPLC-ESI-HRMS analysis, thus suggesting that SxtA has relaxed substrate specificity in vivo. The chemical structures of these products were further verified by tandem mass spectrometry and labelled-precursor feeding with [guanidino-15N2] arginine and [1,2-13C2] acetate. These results indicate that the reactions catalysed by SxtA could give rise to multiple PST variants, including analogues of ecological and pharmacological significance.
- Subject
- anesthetics; guanidinoheptanes; intermediate-A; paralytic shelllfish poisoning; specialized metabolites
- Identifier
- http://hdl.handle.net/1959.13/1439723
- Identifier
- uon:41013
- Identifier
- ISSN:1439-4227
- Language
- eng
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