Beilstein J. Org. Chem.2017,13, 441–450, doi:10.3762/bjoc.13.47
valine and its C-methylation with methionine and the polyol carbons are derived from a glycolysis intermediate, possibly hydroxymalonyl-ACP.
Keywords: biosynthesis; butyrolactol; contiguous polyol; hydroxymalonyl-ACP; polyketide; Streptomyces; tert-butyl; Introduction
Actinomycetes produce structurally
to C-4) and the pentaol (C-5 to C-9) moieties (Figure 3), suggesting that the contiguous polyol system is not formed by methylene hydroxylation. Another possible pathway for 1,2-diol formation is the incorporation of hydroxymalonyl-ACP from a glycolytic intermediate for chain elongation [23]. To
investigate this possibility, we conducted a feeding experiment of [U-13C6]glucose which could label carbons derived from malonyl-CoA and hydroxymalonyl-ACP. In the 13C NMR spectrum, 13C–13C couplings were observed for C-1/C-2, C-3/C-4, C-5/C-6, C-7/C-8 in addition to the carbon pairs C-11/C-12, C-13/C-14, C
Beilstein J. Org. Chem.2017,13, 348–371, doi:10.3762/bjoc.13.39
[39] are employed. However, more recent crystallographic work on the zwittermicin pathway [43] in which hydroxymalonyl-ACP is used as extender unit, has raised some uncertainty over the hydroxymalonyl stereochemistry, as the (2S)-isomer would appear to fit better within the investigated AT structure
stereochemistry can be introduced at several points within the pathways. For example, although fatty acids are constructed primarily from malonyl-CoA units, the AT domains of cis-AT PKSs exhibit specificity towards a number of branched extender units (including methylmalonyl-CoA, ethylmalonyl-CoA, hydroxymalonyl
-ACP, methoxymalonyl-ACP, etc. [15][16]), thus incorporating pendant functionality into the polyketide skeleton (C-2-methyl, C-2-ethyl, C-2-hydroxy and C-2-methoxy groups, respectively). In the case of erythromycin A (1) (Figure 2 and Figure 3), for example, the C-2-methyl groups resulting from use of
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Graphical Abstract
Figure 1:
Structures of clinically-relevant polyketides: erythromycin A (1), azithromycin (2), clarithromycin...