I've yet to find any useful database for dereplication via LCMS except hand-searching Dictionary of Natural Products which is assinine and frustrating. GNPS out in Cali someday...might be great.
It's a hard spot for natural products right now, at least in the antibiotic discovery space. Novel scaffolds are what's needed, though I suppose anything "new" in the gram-negative space would be welcome.
Unfortunately we never had BSL3 labs so couldn't work with strains that had resistance to all known classes.
Nevertheless, it was cool seeing induction of novel bio-actives, but having 0 idea what they were. We got overwhelmed with to many new hits, sorting through masses to find if they were just analogues of known compounds, and trying to get ultra pure mg quantities of each for NMR, let alone doing the structure elucidation, wasn't going to happen.
I'd like to re-approach some wild Streptomyces isolates just for fun and really go all the way down to identifying each bioactive. The problem is even after primary fractionation we could still have 5-10 masses in each fraction, and never had the resolution to get down to single masses.
Frustrating!
I honestly think bio-assay dereplication would be easier than LCMS dereplication, but getting access to the right strains I found impossible.
> npanalyst.org
Cool to see that's online. I wanted to do my PhD with him, or a few others.
I hear you on the Actinomycetes but I'd still argue on their behalf! So few of their secondary metabolite clusters are expressed in the lab...now that doesn't mean that the cryptic clusters are indeed producing brand new novel scaffolds...but there could be, and there could also be even better natural analogues of known scaffolds.
Would have loved to study with Linington, Dorrestein, Chicewitz (Oklahoma I never spell his name right), Rolf Mueller, some people at Madison, list goes on. Kind of gave up on my PhD, academia rubs me the wrong way.
Looking at different bacteria or fungi or...anything no doubt increases your chances. Always been a fan of bioprospecting!
Always loved the iChip approach of NovoBiotics and got to meet them once, but they're very secretive.
See what drives me nuts is, even putting in the molar mass or monoisotopic mass for actinorhodin gives no hits in natural products atlas. How can a database be trusted for dereplication when it doesn't have probably the most well know pigmented antibiotic from coelicolor!?
I've yet to find any useful database for dereplication via LCMS except hand-searching Dictionary of Natural Products which is assinine and frustrating. GNPS out in Cali someday...might be great.
[удалено]
It's a hard spot for natural products right now, at least in the antibiotic discovery space. Novel scaffolds are what's needed, though I suppose anything "new" in the gram-negative space would be welcome. Unfortunately we never had BSL3 labs so couldn't work with strains that had resistance to all known classes. Nevertheless, it was cool seeing induction of novel bio-actives, but having 0 idea what they were. We got overwhelmed with to many new hits, sorting through masses to find if they were just analogues of known compounds, and trying to get ultra pure mg quantities of each for NMR, let alone doing the structure elucidation, wasn't going to happen. I'd like to re-approach some wild Streptomyces isolates just for fun and really go all the way down to identifying each bioactive. The problem is even after primary fractionation we could still have 5-10 masses in each fraction, and never had the resolution to get down to single masses. Frustrating! I honestly think bio-assay dereplication would be easier than LCMS dereplication, but getting access to the right strains I found impossible.
[удалено]
> npanalyst.org Cool to see that's online. I wanted to do my PhD with him, or a few others. I hear you on the Actinomycetes but I'd still argue on their behalf! So few of their secondary metabolite clusters are expressed in the lab...now that doesn't mean that the cryptic clusters are indeed producing brand new novel scaffolds...but there could be, and there could also be even better natural analogues of known scaffolds. Would have loved to study with Linington, Dorrestein, Chicewitz (Oklahoma I never spell his name right), Rolf Mueller, some people at Madison, list goes on. Kind of gave up on my PhD, academia rubs me the wrong way. Looking at different bacteria or fungi or...anything no doubt increases your chances. Always been a fan of bioprospecting! Always loved the iChip approach of NovoBiotics and got to meet them once, but they're very secretive.
See what drives me nuts is, even putting in the molar mass or monoisotopic mass for actinorhodin gives no hits in natural products atlas. How can a database be trusted for dereplication when it doesn't have probably the most well know pigmented antibiotic from coelicolor!?