Knottins can be obtained either
- By extraction from natural sources
[Favel et al, 1989;
Saether et al, 1995;
Hernandez et al, 2000;
Cemazar et al, 2006].
- By chemical synthesis.
- As expressed recombinant proteins
[Camarero et al, 2007;
Krause et al, 2007;
Cui et al, 2007;
Kimura et al, 2006;
Kimura & Camarero, 2005;
Ji et al, 2005;
Schmoldt et al, 2005;
Kratzner et al, 2005;
Escoubas et al, 2003;
Chen et al, 1992].
Recombinant toxin production
Few toxins have been produced as recombinant proteins. Conotoxin MVIIA, which is
used as an analgesic (Ziconotide, commercial name PRIALT) has been expressed in
Escherichia coli as a fusion protein with thioredoxin
[Zhan et al, 2003].
Conotoxin It7a from Conus litteratus has been expressed and purified
in Escherichia coli from a fusion protein with thioredoxin and His-tag
[Pi et al, 2007].
Early synthesis of ω-conotoxin GVIA
As conotoxins are usually small peptides and because many bear post-translational
modifications, solid-phase chemical synthesis is the most used method to produce
conotoxin samples. Early syntheses appeared in the late 80s
[Rivier et al, 1987].