Biology Reference
In-Depth Information
genetic relatedness on the other. It is suggested that LGT and interaction of the specifi c genotype
with environmental conditions play a predominant role in the production of variety of secondary
metabolites (Thacker and Paul, 2004).
Unusual lipopeptides produced as secondary metabolites are characteristic of
L
.
majuscula
.
Amongst these, antillatoxin (ATX) and kalkitoxin (designated as 1) are neurotoxins (Fig. 22; Orjala
et al
., 1995; Berman
et al
., 1999; Yokokawa
et al
., 1999, 2000a,b; Wu
et al
., 2000). ATX is toxic to
fi shes, so termed as ichthyotoxin. It is a cyclic lipopeptide whose total chemical synthesis has been
achieved (Yokokawa
et al
., 1999) but the synthetic sample is not identical in its toxicity to the natural
one (Yokokawa
et al
., 2000a,b). Along with ATX and kalkitoxin, curacin-A has also been identifi ed
as a natural product of
L
.
majuscula
. ATX and kalkitoxin produced a concentration-dependent
neurotoxicity in rat cerebellar granule neurones whereas curacin-A was non-toxic. ATX caused
acute neurotoxicity in short time whereas kalkitoxin produced a delayed neurotoxic response. LC
50
values of 20.1 ± 6.4 and 3.8 ± 1.91 nM were observed for ATX and kalkitoxin, respectively (Berman
et al
., 1999).
L
.
majuscula
from Carribean collections produced kalkitoxin. Complete stereostructure, synthesis
and biological properties of kalkitoxin have been described (Wu
et al
., 2000). It is toxic to common
gold fi sh (
Carassius auratus
, LC
50
, 700 nM), potently toxic to brine shrimp (
Artemia salina
; LC
50
170 nM) and also potently inhibits cell division in fertilized sea urchin embryo assay (IC
50
"25 nM).
Synthetic kalkitoxin also is toxic to the same extent (LC
50
170nM) in brine shrimp assay. Natural
kalkitoxin showed exceptional neurotoxicity in cell cultures of rat neurons with LC
50
of 3.86 nM.
Besides, it is also shown to be a potent blocker of the voltage senstive Na
+
channel in mouse neuro-2
a cells (EC
50
= 1 nM). The biosnthesis of kalkitoxin is through polyketide/nonribosomal peptide
synthetase pathway (Wu
et al
., 2000).
In cerebellar granule cells exposed to ATX (100nM), a rapid increase in Ca
2+
was antagonized by
tetrodotoxin in a concentration-dependent manner. Further, ATX induced allosteric enhancement of
[H
3
] batrachotoxin binding to site 2 of α-subunit. ATX also produced a strong synergistic binding in
combination with brevetoxin for site 5 on the voltage gated Na
+
channel. Thus these results suggest
that ATX is an activator of voltage-gated sodium channels (Li
et al
., 2001).
III. DERMATOTOXINS
Aplysiatoxins (ATs), debromoaplysiatoxins (DATs) and lyngbyatoxins (LA-A, B, C) produced by
species of benthic cyanobacteria like
Oscillatoria
(
O
.
nigroviridis
),
Lyngbya
(
L
.
majuscula
) and
Schizothrix
(
S
.
calcicola
) and
Planktothrix
are included here (Moore, 1977; Mynderse
et al
., 1977; Chorus and
Bartram, 1999). ATs and DATs are tumor promoters and activate protein C kinase (Mynderse
et al
.,
1977; Fujiki
et al
., 1990). ATs and DATs cause dermatitis but LAs besides causing dermatitis are also
responsible for oral or gastrointestinal infl ammation (Cardellina
et al
., 1979). These disorders were
reported in swimmers in tropical and sub-tropical waters caused by
L
.
majuscula
(Osborne
et al
., 2001).
On Winward beaches of Hawaii in 1958 and on beaches in Okinawa (Japan) in 1968 cases of acute
dermatitis (also known as “swimmers's itch”) were reported (Moikeha and Chu, 1971; Hoshimoto
et al
., 1976; Burke and Tester, 2002). A subcutaneous infl ammation with signs of erythema, blisters
and desquamation occurred within 12 h of exposure to the cyanobacterium. ATs are toxic to mice
at a dose of 0.3 mg kg
-1
body weight (Moore, 1977).
