Biology Reference
In-Depth Information
nodularin. The linear nodularin and geometrical isomer of Nod-R have also been isolated. Of the
eight variants [dhb
5
]-nodularin and [MeAdda]-nodularin are the new variants. Of these, seven are
reported to be produced by marine forms of
No
.
spumigena
while one nodularin has its origin from
a freshwater strain
Nodularia
PCC 7804.
(ii)
Biosynthesis
: Labelling studies have shown that nodularin biosynthesis is a mixed PKS-NRPS
pathway (Moore
et al
., 1991; Rinehart
et al
., 1994). Based on these results and those of
mcy
gene cluster
(Tillett
et al
., 2000) it has now been possible to predict the biosynthetic pathway of nodularin. Peptide
synthetase and PKS gene homologues were identifi ed in various strains of
Nodularia
isolated from
globally diverse locations by degenerate PCR technique (Moffi tt and Neilan, 2001). Various strains
(21) of
No
.
spumigena
,
No
.
harveyana
and
No
.
sphaerocarpa
were subjected to 16S rDNA sequence
analysis to fi nd out their interrelationships.
No
.
spumigena
represented a distinct cluster producing
nodularin while the other two species formed a second cluster representing the benthic non-toxic
types (Moffi tt
et al
., 2001). Nodularin synthetase gene cluster of
No
.
spumigena
SOR 10 is a 48-kb cluster
that consists of 9 genes,
nda A
to
nda I
and it is transcribed bidirectionally from a regulatory promoter
Figure 9:
Structure of nodularin. Nodularin is a cyclic pentapeptide (MW 619). The L-Arg residue of nodularin may be
replaced with a homoarginine (nodularin-Har) or valine residue (motuporin).
region located in between
nda A
and
nda C
(Fig. 7A). NRPS, PKS modules and tailoring enzymes are
synthesized by this gene cluster. The presence of transposases fl anking the
nda
gene cluster is akin to
the
mcy
gene cluster. Comparative and phylogenetic analysis of
mcy
and
nda
gene clusters revealed
that nodularin gene cluster might have evolved from
mcy
gene cluster (Moffi tt and Neilan, 2004).
The probable functions of the enzymes encoded by the
nda
gene cluster were compared to those of
the homologous proteins of
mcy
gene cluster to assign their functions and catalytic activities. ORFs
nda CDEF
encode enzymes for biosynthesis of Adda while
nda GHAB
encode enzymes responsible
for peptide synthesis, cyclization and transport (Moffi tt and Neilan, 2004). There are four NRPS
modules identifi ed for nodularin. The active sites of D-Glu and D-MeAsp A domains are identical
to MC synthetases. The active sites of
nda A
activates and methylates L-Thr as a precursor of Medhb
and has little homology to the active site of
mcy A
. Conversion of Me-Thr to Medhb occurs via
nda
H
enzyme similar to the conversion of Me-Ser to MeDha (Moffi tt and Neilan, 2004).
