Biomedical Engineering Reference
In-Depth Information
O
H
2
N
OH
R
1
R
1
NH
CO
2
H
O
R
3
O
O
N
H
2
N
OH
H
H
O
NH
R
2
O
O
HN
O
S. coelicolor
HO
2
C
X
N
CO
2
H
R
5
O
N
HO
2
C
O
O
O
O
H
2
NOC
NH
OH
O
H
2
N
N
OH
H
H
O
R
3
O
NH
R
2
CO
2
H
H
R
3
36
(R
1
= OH; R
2
= Me; R
3
= H; X = O; R
5
=
n
-Pr)
37
(R
1
= H; R
2
= Me; R
3
= H; X = O; R
5
=
n
-Pr)
38
(R
1
= F; R
2
= Me; R
3
= H; X = O; R
5
=
n
-Pr)
39
(R
1
= OH; R
2
= CF
3
; R
3
= H; X = O; R
5
=
n
-Pr)
40
(R
1
= OH; R
2
= Et; R
3
= H; X = O; R
5
=
n
-Pr)
41
(R
1
= OH; R
2
= Me; R
3
= OH; X = O; R
5
=
n
-Pr)
42
(R
1
= OH; R
2
= Me; R
3
= F; X = O; R
5
=
n
-Pr)
43
(R
1
= OH; R
2
= Me; R
3
= H; X = H; R
5
=
n
-Pr)
44
(R
1
= OH; R
2
= Me; R
3
= H; X = H; R
5
= Et)
O
X
R
5
SNAC
SCHEME 14.8
Precursor-directed biosynthesis of selected analogues of calcium-dependent
antibiotic.
yield. With longer precursors, there was no detectable production of the expected
compounds. This, as is the case with many such systems, likely speaks to the
specificity of the first condensation domain, responsible for the coupling of the
N
-
acyl serine and the threonine present on the module 2
pcp
[50].
With the approval of daptomycin for clinical use in the treatment of vanco-
mycin-resistant bacteria, interest in the development of novel lipopeptides has greatly
increased in the past several years. As illustrated in the studies presented here, it
appears that precursor-directed biosynthesis will be an integral tool in the production
of the next generation of lipopeptide antibiotics.
14.4.2.4. Beauvericin Beauvericin
, a nonribosomal peptide isolated from a
series of filamentous fungi including
Beauveria bassiana
and
Paecilomyces tenuipes
,
is unique among the nonribosomal peptides that will be discussed in this chapter. It
belongs to a subclass of compounds termed the depsipeptides that, despite being the
product of an NRPS, are not, strictly speaking, peptides but rather cyclic compounds
45
Search WWH ::
Custom Search