Biology Reference
In-Depth Information
Choi
2-carboxy-6-hydroxyoctahydroindole
CM
C-methyltransferase domain
DH
dehydratase domain
E
epimerase domain
EP
epimerase domain
ER
enoylreductase domain
KR
ketoreductase domain
KS
ketosynthase domain
MIB
2-methylisoborneol
MT
methyltransferase domain
NRP
nonribosomal peptide
NRPS
nonribosomal peptide synthase
OM
O-methyltransferase domain
PCP
peptidyl carrier protein
PK
polyketide
PK/NRP
polyketide/nonribosomal peptide hybrid
PKS
polyketide synthase
PKS/NRPS
polyketide synthase/nonribosomal peptide synthase hybrid
RP
ribosomal peptide
TE
thioesterase domain
.
1. INTRODUCTION
Natural products, including microbial secondary metabolites, have
played a prominent role in the development of drugs to treat infections,
cancers and many other diseases (
Newman & Cragg, 2012
). They have also
inspired synthetic chemists because of the tremendous chemical diver-
sity encountered in these metabolites produced by living organisms, and
because of the interest in modifying the structure of natural products to
obtain new molecules with superior bioactivities. It is thus not surprizing
that this scientific field is still very active (
Walsh & Fischbach, 2010
).
Historically, natural products were isolated from plants, marine organisms
and microorganisms, and their chemical structure was then elucidated, and
their biological activity was screened. This traditional approach is still used and
is still necessary to find new bioactive molecules and to prove the structure of
the isolated metabolite. However, the natural product field made an important
step when the genes coding for the enzymes involved in the biosynthesis of the
natural antibiotic erythromycin, a macrocyclic polyketide (PK), were identified
and sequenced (
Cortes, Haydock, Roberts, Bevitt, & Leadlay, 1990
;
Donadio,
Staver, McAlpine, Swanson, & Katz, 1991
). The core structure of this antibiotic
is produced by three giant polyketide synthases (PKSs) that are modular with
each module responsible for the introduction of two carbons from acetate.
