The biosynthetic pathway of kainoids.
Date
1994
Authors
Ramsey, Una Patricia.
Journal Title
Journal ISSN
Volume Title
Publisher
Dalhousie University
Abstract
Description
Domoic acid and kainic acid are neurotoxic amino acids that belong to a group of compounds called the kainoids. The pathway of domoic acid biosynthesis was investigated in the photosynthetic single-celled plankton or diatom Pseudonitzschia pungens f. multiseries using both $\sp $C- and $\sp $C-labelled precursors. Labelling with (1,2-$\sp $C) -acetate revealed that domoic acid is biosynthesized by the condensation of an isoprenoid chain with a citric acid cycle product. The addition of (1,2-$\sp $C) -acetate early and late during exponential growth did not affect the resulting $\sp $C enrichment pattern. Further studies with (2-$\sp $C, $\rm\sp2H\sb3$) -acetate showed that the hydroxyl group of isocitrate is converted to a carbonyl group before the transamination reaction, suggesting that the citric acid cycle product is a derivative of glutamate. (1,5-$\sp $C) -Citrate, (1-$\sp $C) -$\alpha$-ketoglutarate and L (1-$\sp $C) -glutamate were incorporated into domoic acid at low levels.
The Palmaria palmata mutant GM, a known producer of kainic acid, was examined for possible intermediates of kainic acid biosynthesis. An unknown secondary amino acid was isolated and identified as 1$\sp\prime$-hydroxydihydrokainic acid. This compound is probably formed by hydration of kainic acid and is unlikely to be a precursor of kainic acid. 1$\sp\prime$-Hydroxydihydrokainic acid is able to chelate both calcium and copper and may function as a metal detoxifier within the cells.
Two protein prenylation inhibitors, gliotoxin and (+)-limonene did not inhibit domoic acid biosynthesis in P. pungens f. multiseries. (+)-Limonene at a final concentration of 0.5 $\mu$M did result in an increase in domoic acid production. Preliminary kainic acid prenyltransferase assays with (1,5-$\sp $C) -citrate, (1-$\sp $C) -$\alpha$-ketoglutarate or L (1-$\sp $c) -glutamate added did not produce $\sp $C-labelled kainic acid.
Thesis (Ph.D.)--Dalhousie University (Canada), 1994.
The Palmaria palmata mutant GM, a known producer of kainic acid, was examined for possible intermediates of kainic acid biosynthesis. An unknown secondary amino acid was isolated and identified as 1$\sp\prime$-hydroxydihydrokainic acid. This compound is probably formed by hydration of kainic acid and is unlikely to be a precursor of kainic acid. 1$\sp\prime$-Hydroxydihydrokainic acid is able to chelate both calcium and copper and may function as a metal detoxifier within the cells.
Two protein prenylation inhibitors, gliotoxin and (+)-limonene did not inhibit domoic acid biosynthesis in P. pungens f. multiseries. (+)-Limonene at a final concentration of 0.5 $\mu$M did result in an increase in domoic acid production. Preliminary kainic acid prenyltransferase assays with (1,5-$\sp $C) -citrate, (1-$\sp $C) -$\alpha$-ketoglutarate or L (1-$\sp $c) -glutamate added did not produce $\sp $C-labelled kainic acid.
Thesis (Ph.D.)--Dalhousie University (Canada), 1994.
Keywords
Chemistry, Biochemistry.