7AYX

Structure of the cytochrome P450 AryC from Streptomyces roseosporus NRRL 15998

Summary for 7AYX

• Entry DOI: 10.2210/pdb7ayx/pdb
• Descriptor: Cytochrome P450 113A1, PROTOPORPHYRIN IX CONTAINING FE, SULFATE ION, ... (4 entities in total)
• Functional Keywords: cytc p450, oxidase, arylomycin biosynthesis, cytosolic protein
• Biological source: Streptomyces filamentosus NRRL 15998
• Total number of polymer chains: 2
• Total formula weight: 94753.80

Authors

Schneider, S.,Schaefers, F.,Gulder, T.A.M. (deposition date: 2020-11-13, release date: 2021-10-27, Last modification date: 2024-01-31)

Primary citation

Aldemir, H.,Shu, S.,Schaefers, F.,Hong, H.,Richarz, R.,Harteis, S.,Einsiedler, M.,Milzarek, T.M.,Schneider, S.,Gulder, T.A.M.
Carrier Protein-Free Enzymatic Biaryl Coupling in Arylomycin A2 Assembly and Structure of the Cytochrome P450 AryC.
Chemistry, 28:e202103389-e202103389, 2022

PubMed Abstract: The arylomycin antibiotics are potent inhibitors of bacterial type I signal peptidase. These lipohexapeptides contain a biaryl structural motif reminiscent of glycopeptide antibiotics. We herein describe the functional and structural evaluation of AryC, the cytochrome P450 performing biaryl coupling in biosynthetic arylomycin assembly. Unlike its enzymatic counterparts in glycopeptide biosynthesis, AryC converts free substrates without the requirement of any protein interaction partner, likely enabled by a strongly hydrophobic cavity at the surface of AryC pointing to the substrate tunnel. This activity enables chemo-enzymatic assembly of arylomycin A2 that combines the advantages of liquid- and solid-phase peptide synthesis with late-stage enzymatic cross-coupling. The reactivity of AryC is unprecedented in cytochrome P450-mediated biaryl construction in non-ribosomal peptides, in which peptidyl carrier protein (PCP)-tethering so far was shown crucial both in vivo and in vitro.

PubMed: 34725865
DOI: 10.1002/chem.202103389

Experimental method

X-RAY DIFFRACTION (2.53 Å)