Biology Reference
In-Depth Information
Figure 6.13
Thestructureofcryptophycin1andtheproposedbiosynthesis.Theactual
starterofthePKSCrpA,indicatedasRontheigure,isnotknown.Thedomainabbrevia-
tionsaredeinedintheabbreviationslist.
agents. The biosynthesis of cryptophycin 1 has been studied using feed-
ing experiments that served to identify the biosynthetic gene cluster in
Nostoc
sp. ATCC 53789 (
Magarvey et al., 2006
). The
crp
cluster consists
of eight genes with four genes coding for PKSs and NRPSs (
Fig. 6.14
).
The biosynthesis probably starts with the PKS CrpA although, like for
microcystin biosynthesis, there are some doubts concerning the identity
of the real starter (
Fig. 6.13
). The chain is then elongated on the CrpB, C
and D synthases and the last TE domain performs the macrocyclization.
Then, tailoring enzymes, like the epoxidase and the halogenase, modify
the molecule to give cryptophycin 1. Some steps have been reconsti-
tuted in vitro and the isolated enzymes have been used to prepare cryp-
tophycin in a chemoenzymatic way (
Ding, Seufert, Beck, & Sherman,
2008
,
2011
).
