P450 enzyme KwwB installs non-native Tyr–Trp cross-link in cyclic peptides
The enzyme also tolerated leader peptide mutations at positions -11 to -2, failing only at the conserved proline at position -4.
PR
By Priya Raman · Science Reporter
Sep 28 09:52 ETSource: Nature
The wire
- 01Researchers report that P450 cyptide synthase KwwB from Kitasatospora sp. GAS204B catalyzes a non-native cross-link between Tyr-C3 and Trp-N1 at a YxW motif.
- 02Macrocyclization improves proteolytic stability, cell permeability and binding affinity, and promiscuous macrocyclases are a route to new cyclic peptide drug candidates.
- 03This is enzymology in a biosynthetic system, not a therapeutic candidate; translation to any specific drug scaffold remains untested.
From the source
Read at nature.comP450 cyptide synthase KwwB catalyzes non-native cross-link at Tyr-C3–Trp-N1 and tolerates leader peptide mutations
Cyptides refer to a rapidly growing class of ribosomally synthesized and post-translationally modified peptides (RiPPs) containing biaryl cyclophanes installed by P450 enzymes. Here, we further investigated P450 cyptide synthase KwwB from Kitasatospora sp. GAS204B, which expands the KwwB-catalyzed chemical repertoire to non-native cross-link between Tyr-C3 and Trp-N1 at the YxW motif. In addition,
