Chemistry Reference
In-Depth Information
O
OH
O
O
HO
+HS-ACP/-
C
oA
acyltransferase
(domain)
OH
CoA
CoA
P
KS
+
+
N
R
S
R
S
O
O
O
acyl-CoA
acyl-CoA
O
O
OMe
OH
O
Erythromycin A
OH
OH
+ATP/-PPi
+ HS-PCP/-A
M
P
adenylation
domain
OH
O
O
H
2
N
HO
N
RPS
++
H
2
N
H
2
N
CPC
O
OH
S
O
O
Cl
R
R
aminoacyl-PCP
O
O
O
amino acid
HO
OH
Cl
O
O
O
H
N
O
N
H
H
N
NHCH
3
H
N
H
HN
HOOC
OH
2
N
O
O
OH
HO
OH
Vancomycin
OH
HO
HOCH
2
O
O-PO
3
H
2
HOCH
2
O
O-dNDP
O
HO
+ dTTP/-P
P
i
glucose-1-phosphate
nucleotidyltransferase
HO
H
2
N
OH
NH
2
O
+
+G
T
++
HO
OH
HO
OH
HO
OH
O
O
NH
2
OH
OH
H
2
N
glucose-1 phosphate
dNDP-glucose
Kanamycin A
CH
3
O
OH
HO
CH
3
Cl
+ 3ATP/- 3
A
DP, -CO
2
Cl
OH
H
2
C
O-PO
3
H-PO
3
H
2
(phospho)mevalonate
kinases,
diphosphomevalonate
decarboxylase
COOH
P
DS
+
+
O
OH
mevalonate
isopentenyl diphosphate
O
Napyradiomycin A
Figure 11.2
Examples on activation and incorporation of “building blocks” (shown
in bold lines) into the scaffolds of polyketide, nonribosomal peptide, aminoglycoside,
and terpene antibiotics. Common enzymes responsible for scaffolds' assembly:
PKS
;
NRPS
;
GT
, glycosyltransferase;
PDS
, polyprenyl diphosphate synthase. (
++
) indicate
that additional enzymatic reactions required to synthesize the antibiotic molecule.
NRPS (22). Most nonribosomally synthesized peptide antibiotics contain nonpro-
teinogenic amino acids, which are synthesized by dedicated enzymes (23).
“Building blocks” in the biosynthesis of aminoglycoside and oligosac-
charide antibiotics scaffolds (e.g., kanamycin and avilamycin) are derived
from monosaccharide-1-phosphates, which are converted to deoxysugar
nucleotidyldiphosphates (dNDP-deoxysugars) via a series of enzymatic steps.
