Biology Reference
In-Depth Information
4.4. Toxins and Other Secondary Metabolites from Marine
Cyanobacteria
Marine filamentous cyanobacteria produce a variety of secondary metab-
olites with interesting chemical structures and biological activities. These
microorganisms have been largely used as a source of new drugs with a
special emphasis on anti-cancer drugs. However, if many new metabolites
have been identified, their biosynthesis remains largely unknown. But, sev-
eral research groups have largely contributed to the understanding at the
genomic and biochemical level of the biosynthesis of some remarkable
marine cyanobacterial metabolites (
Jones et al., 2010
;
Moore, Corbett,
Patterson, & Valeriote, 1996
;
Nunnery et al., 2010
). They have shown that
the biosynthetic pathways are very diverse including NRPS, PKS, and
NRPS-PKS hybrids. Excellent reviews cover this fascinating field and we
have thus summarized here some interesting cases. The reader is referred to
recent reviews covering the biosynthesis of lyngbyatoxins A-C, hectochlo-
rin and barbamide (
Jones, Gu, Sorrels, Sherman, & Gerwick, 2009
;
Jones
et al., 2010
;
Nunnery et al., 2010
).
4.4.1. Apratoxins
Apratoxins A-G share a core cyclic lipopeptide structure that is in fact a
PK/NRP hybrid. These secondary metabolites have been extracted from
diverse strains of
Lyngbya bouillonii
that are marine cyanobacteria and they
show interesting cytotoxic bioactivities. The biosynthetic gene cluster for
apratoxin A has recently been identified by using an interesting combina-
tion of different approaches by Gerwick and co-workers (
Grindberg et al.,
2011
). These authors used a single cell as a PCR template to amplify the
whole genome of the producer. The genome was then sequenced and the
cluster was then identified using diverse screenings. The 58-kb
apr
cluster
contains 12 genes, among which eight are coding for PKS or NRPS or
hybrids. A biosynthetic pathway was proposed based on the bioinformatics
analysis of the cluster sequence.
4.4.2. Curacins
Curacin A is a mixed PK/NRP produced by
Lyngbya majuscula
, contain-
ing interesting chemical motif: a cyclopropane ring and a thiazole ring
derived from cysteine. This metabolite is of considerable interest because
it is an antiproliferative compound with antitubulinin activity. Thus,
analogues of curacin A might be used as anti-cancer drugs. The bio-
synthesis of this metabolite has been elucidated by feeding experiments
