18 research outputs found
Living GenoChemetics by hyphenating synthetic biology and synthetic chemistry in vivo
Marrying synthetic biology with synthetic chemistry provides a powerful approach toward natural product diversification, combining the best of both worlds: expediency and synthetic capability of biogenic pathways and chemical diversity enabled by organic synthesis. Biosynthetic pathway engineering can be employed to insert a chemically orthogonal tag into a complex natural scaffold affording the possibility of site-selective modification without employing protecting group strategies. Here we show that, by installing a sufficiently reactive handle (e.g., a C–Br bond) and developing compatible mild aqueous chemistries, synchronous biosynthesis of the tagged metabolite and its subsequent chemical modification in living culture can be achieved. This approach can potentially enable many new applications: for example, assay of directed evolution of enzymes catalyzing halo-metabolite biosynthesis in living cells or generating and following the fate of tagged metabolites and biomolecules in living systems. We report synthetic biological access to new-to-nature bromo-metabolites and the concomitant biorthogonal cross-coupling of halo-metabolites in living culture
Posterior epidural migration of sequestered lumbar disc fragments. Report of two cases.
The posterior epidural migration of sequestered lumbar disc fragments is an uncommon event. The authors report two such cases in which patients presented with either intense radicular pain or cauda equina syndrome. The radiological characteristics were the posterior epidural location and the ring enhancement of the mass after injection of contrast material. The major diagnostic pitfalls are discussed
Double Bond Stereochemistry Influences the Susceptibility of Short‑Chain Isoprenoids and Polyprenols to Decomposition by Thermo‑Oxidation
Alcohols are common constituents of
living cells. They are usually assigned a role in the adaptation
of the cell to environmental stimuli, and this process
might give rise to their oxidation by reactive oxygen
species. Moreover, cellular isoprenoids may also undergo
various chemical modifications resulting from the physicochemical
treatment of the tissues, e.g., heating during food
processing. Susceptibility of isoprenoid alcohols to heat
treatment has not been studied in detail so far. In this study,
isoprenoid alcohols differing in the number of isoprene units
and geometry of the double bonds, β-citronellol, geraniol,
nerol, farnesol, solanesol and Pren-9, were subjected to
thermo-oxidation at 80 °C. Thermo-oxidation resulted in the
decomposition of the tested short-chain isoprenoids as well
as medium-chain polyprenols with simultaneous formation
of oxidized derivatives, such as hydroperoxides, monoepoxides,diepoxides and aldehydes, and possible formation of oligomeric derivatives. Oxidation products were monitored by GC-FID, GC-MS, ESI-MS and spectrophotometric methods. Interestingly, nerol, a short-chain isoprenoid with a double bond in the cis (Z) configuration, was more oxidatively stable than its trans (E) isomer, geraniol. However, the opposite effect was observed for medium-chain polyprenols, since Pren-9 (di-trans-poly-cis-prenol) was more susceptible to thermo-oxidation than its all-trans isomer, solanesol. Taken together, these results experimentally confirm that both short- and long-chain polyisoprenoid alcohols are prone to thermo-oxidation