Enaminone formation drives the coupling of biosynthetic pathways to generate cyclic lipopeptides
A family of novel cyclic lipopeptides named tasikamides A H (Tsk A H) were discovered recently in Streptomyces tasikensis P46. Aside from the unique cyclic pentapeptide scaffold shared by the tasikamides, Tsk A C contain a hydrazone bridge that connects the cyclic pentapeptide to the lipophil...
| Main Authors: | , , , |
|---|---|
| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2022
|
| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/163433 |
| Summary: | A family of novel cyclic lipopeptides named tasikamides A H
(Tsk A H) were discovered recently in Streptomyces tasikensis
P46. Aside from the unique cyclic pentapeptide scaffold shared
by the tasikamides, Tsk A C contain a hydrazone bridge that
connects the cyclic pentapeptide to the lipophilic alkyl 5-
hydroxylanthranilate (AHA) moiety. Here we report the production
of tasikamides I K (Tsk I K) by a mutant strain of S.
tasikensis P46 that overexpresses two pathway-specific transcription
regulators. Unlike Tsk A C, Tsk I K feature a rare
enaminone-bridge that links the cyclic peptide scaffold to the
AHA moiety. Our experimental data suggest that Tsk I K are
generated by the coupling of two biosynthetic pathways via a
nonenzymatic condensation reaction between an arylamine
and a β-keto aldehyde-containing precursor. The results underscore
the nucleophilic and electrophilic reactivity of the β-keto
aldehyde moiety and its ability to |
|---|