2 research outputs found
Improving Natural Products Identification through Targeted LC-MS/MS in an Untargeted Secondary Metabolomics Workflow
Tandem mass spectrometry is a widely
applied and highly sensitive
technique for the discovery and characterization of microbial natural
products such as secondary metabolites from myxobacteria. Here, a
data mining workflow based on MS/MS precursor lists targeting only
signals related to bacterial metabolism is established using LC-MS
data of crude extracts from shaking flask fermentations. The devised
method is not biased toward specific compound classes or structural
features and is capable of increasing the information content of LC-MS/MS
analyses by directing fragmentation events to signals of interest.
The approach is thus contrary to typical auto-MS<sup>2</sup> setups
where precursor ions are usually selected according to signal intensity,
which is regarded as a drawback for metabolite discovery applications
when samples contain many overlapping signals and the most intense
signals do not necessarily represent compounds of interest. In line
with this, the method described here achieves improved MS/MS scan
coverage for low-abundance precursor ions not captured by auto-MS<sup>2</sup> experiments and thereby facilitates the search for new secondary
metabolites in complex biological samples. To underpin the effectiveness
of the approach, the identification and structure elucidation of two
new myxobacterial secondary metabolite classes is reported
Aetheramides A and B, Potent HIV-Inhibitory Depsipeptides from a Myxobacterium of the New Genus “<i>Aetherobacter</i>”
Aetheramides are structurally distinctive cyclic peptides isolated from a novel myxobacterial genus proposed to be termed “<i>Aetherobacter”</i>. The structures were solved by a combination of NMR analyses, quantum mechanical calculations, and chemical derivatizations. Aetheramides which contain a unique polyketide moiety and two amino acid residues potently inhibited HIV-1 infection with IC<sub>50</sub> values of ∼0.015 μM. Furthermore aetheramides showed cytostatic activity against human colon carcinoma (HCT-116) cells with IC<sub>50</sub> values of 0.11 μM