Biology Reference
In-Depth Information
4.5.1. Cyanobactins
Cyanobactins, such as patellamide or microcyclamide, are small cyclic RPs
produced by cyanobacteria of different genera. These peptides usually
contain oxazoline or thiazoline motifs or their oxidized derivatives, oxa-
zole or thiazole, although there are examples of cyanobactins that do not
contain any of these heterocycles (
Sivonen et al., 2010
). Cyanobactins are
also sometimes prenylated on amino acid side chains of serine, threonine
or tyrosine. These peptides show very diverse biological activities such as
inhibition of proteases, or cytotoxicity. The cluster of genes responsible for
the biosynthesis of patellamide (
Fig. 6.15
) was first identified in
Prochloron
didemnii
(
Schmidt et al., 2005
), and later, homologous cyanobactin clus-
ters have been found in many cyanobacterial genomes, by genome mining
(
Donia & Schmidt, 2011
). Indeed, the biosynthetic genes are conserved,
although with some differences from genus to genus and strain to strain
(
Fig. 6.15
). The biosynthesis of these peptides is not fully understood but
the main steps have been deciphered (
McIntosh, Donia, Nair, & Schmidt,
2011
;
McIntosh, Donia, Schmidt et al., 2010
;
McIntosh, Robertson, et al.,
2010
;
McIntosh & Schmidt, 2010
). The precursor, PatE in the case of patel-
lamide, bears an N-terminal conserved leader sequence, followed by two
sequences that will give the patellamide A and C, flanked by conserved
recognition sequence motifs for the protease (
Fig. 6.16
). The precursor is
first processed by the enzyme, PatD, responsible for the heterocyclizations of
serine, threonine and cysteine residues. Then, the protease PatA cleaves off
the N-terminal part of the precursor after the GLEAS or GVEPS recogni-
tion sequences. Then the PatG protease cleaves off the C-terminal AYDGE
Figure 6.15
ThestructureofpatellamideAandCandoftheircommonprecursor.The
leadersequenceisitalicized,theproteaserecognitionsequencesareinboldtype,and
thecyanobactinsequencesareunderlined.
