5 research outputs found
Engineering of a Synthetic Metabolic Pathway for the Assimilation of (d)‑Xylose into Value-Added Chemicals
No full textA synthetic pathway for (d)-xylose assimilation was stoichiometrically
evaluated and implemented in Escherichia coli strains. The pathway proceeds via isomerization of (d)-xylose
to (d)-xylulose, phosphorylation of (d)-xylulose
to obtain (d)-xylulose-1-phosphate (X1P), and aldolytic cleavage
of the latter to yield glycolaldehyde and DHAP. Stoichiometric analyses
showed that this pathway provides access to ethylene glycol with a
theoretical molar yield of 1. Alternatively, both glycolaldehyde and
DHAP can be converted to glycolic acid with a theoretical yield that
is 20% higher than for the exclusive production of this acid via the
glyoxylate shunt. Simultaneous expression of xylulose-1 kinase and
X1P aldolase activities, provided by human ketohexokinase-C and human
aldolase-B, respectively, restored growth of a (d)-xylulose-5-kinase
mutant on xylose. This strain produced ethylene glycol as the major
metabolic endproduct. Metabolic engineering provided strains that
assimilated the entire C2 fraction into the central metabolism or
that produced 4.3 g/L glycolic acid at a molar yield of 0.9 in shake
flasks
Total Synthesis and Structure Assignment of the Relacidine Lipopeptide Antibiotics and Preparation of Analogues with Enhanced Stability
No full textThe unabated rise of antibiotic resistance has raised
the specter
of a post-antibiotic era and underscored the importance of developing
new classes of antibiotics. The relacidines are a recently discovered
group of nonribosomal lipopeptide antibiotics that show promising
activity against Gram-negative pathogens and share structural similarities
with brevicidine and laterocidine. While the first reports of the
relacidines indicated that they possess a C-terminal five-amino acid
macrolactone, an N-terminal lipid tail, and an overall positive charge,
no stereochemical configuration was assigned, thereby precluding a
full structure determination. To address this issue, we here report
a bioinformatics guided total synthesis of relacidine A and B and
show that the authentic natural products match our predicted and synthesized
structures. Following on this, we also synthesized an analogue of
relacidine A wherein the ester linkage of the macrolactone was replaced
by the corresponding amide. This analogue was found to possess enhanced
hydrolytic stability while maintaining the antibacterial activity
of the natural product in both in vitro and in vivo efficacy studies
