A Genomic View of Secondary Metabolite Production in Cyanobacteria - Advances in Botanical Research - page 205

Interestingly, P. agardhii NIVA-CYA 126/8 lacks the mcyF and mcyI genes,
and it produces a microcystin variant containing D-aspartate in position 3. It
is unclear how this cyanobacterium produces D-aspartate. The last enzyme,
McyC catalyses the condensation of L-arginine and the final cyclization
step, performed by the thioesterase (TE) domain. The mcyH gene prob-
ably codes for an ABC exporter and its inactivation caused an important
decrease in the production of microcystin ( Pearson, Hisbergues, Borner,
Dittmann, & Neilan, 2004 ). In P. agardhii NIVA-CYA 126/8, another gene
mcyT codes for a type-II TE likely involved in proofreading functions by
hydrolysing misprimed PCP and acyl carrier protein (ACP) domains in the
microcystin synthase ( Christiansen, Molitor, Philmus, & Kurmayer, 2008 ).
As noted above, more than 90 variants of microcystins have been identi-
fied. Axenic strains containing one mcy cluster produce two to four variants
that differ in positions 2 (Leu or Arg), 3 ( erythro -methyl-D-Asp or D-Asp)
and 7 ( N -methyl-Dha or Dha). Thus, the adenylation (A) domains of McyB
must show some relaxed specificity and the methylation domain of McyA
must be sometimes inactive. Within species and genera, the origin of the
variants probably comes from recombination events in the mcy genes and, in
particular, in the sequence coding for the A domains ( Kaasalainen et al., 2012 ;
Tooming-Klunderud, Fewer, et al., 2008 ; Tooming-Klunderud, Mikalsen,
et al., 2008 ). These mutations will influence the amino acid activated at each
position, leading to microcystin variants.
Nodularins are nonribosomal cyclic pentapeptides closely related to
microcystins in terms of structure and biosynthesis. They are produced by
cyanobacteria of the genus Nodularia , and, like microcystins, are hepato-
toxic. They contain the Adda residue, like microcystins, and several variants
have been identified, with various degree of methylation. The biosynthetic
gene cluster, nda , has been identified in Nodularia spumigena and it shares
strong similarities with the mcy gene cluster ( Moffitt & Neilan, 2004 ). It has
been suggested that the nda genes are recently derived from the mcy genes
( Rantala et al., 2004 ).
4.1.2. The neurotoxins anatoxin-a, homoanatoxin-a, and saxitoxins
Anatoxin-a and homoanatoxin-a ( Fig. 6.4 ) are two potent neurotoxins
produced by freshwater cyanobacteria of different genera such as Ana-
baena , Aphanizomenon , Oscillatoria , Phormidium , Cylindrospermum , or Raph-
idiopsis ( Osswald, Rellan, Gago, & Vasconcelos, 2007 ). These alkaloids act
as potent agonist of the muscular nicotinic acetylcholine receptor provok-
ing muscle paralysis and respiratory failure ( Wonnacott & Gallagher, 2006 ).