8HK0
Crystal structure of Fic32-33 complex from Streptomyces ficellus NRRL 8067
Summary for 8HK0
| Entry DOI | 10.2210/pdb8hk0/pdb |
| Descriptor | Dehydrogenase, Acyl-CoA dehydrogenase, FLAVIN-ADENINE DINUCLEOTIDE, ... (5 entities in total) |
| Functional Keywords | biosynthetic protein |
| Biological source | Streptomyces ficellus More |
| Total number of polymer chains | 4 |
| Total formula weight | 160472.32 |
| Authors | |
| Primary citation | Cheng, Y.,Yi, X.,Zhang, Y.,He, Q.,Chen, D.,Cao, W.,Fang, P.,Liu, W. Oxidase Heterotetramer Completes 1-Azabicyclo[3.1.0]hexane Formation with the Association of a Nonribosomal Peptide Synthetase. J.Am.Chem.Soc., 145:8896-8907, 2023 Cited by PubMed Abstract: Ficellomycin, azinomycins, and vazabitide A are nonribosomal peptide natural products characterized by an amino acid unit that contains a similar 1-zaiyclo[3.1.0]exane (ABCH) pharmacophore. This unit is derived from imino-ihydroxy-eptanic acid (DADH); however, the process through which linear DADH is cyclized to furnish an ABCH ring system remains poorly understood. Based on the reconstitution of the route of the ABCH-containing unit by blending genes/enzymes involved in the biosynthesis of ficellomycin and azinomycins, we report that ABCH formation is completed by an oxidase heterotetramer with the association of a nonribosomal peptide synthetase (NRPS). The DADH precursor was prepared in to produce a conjugate subjected to enzymatic hydrolysis for offloading from an amino-group carrier protein. To furnish an aziridine ring, DADH was processed by C7-hydroxyl sulfonation and sulfate elimination-coupled cyclization. Further cyclization leading to an azabicyclic hexane pharmacophore was proved to occur in the NRPS, where the oxidase heterotetramer functions and catalyzes α,β-dehydrogenation to initiate the formation of a fused five-membered nitrogen heterocycle. The identity of ABCH was validated by utilization of the resultant ABCH-containing unit in the total biosynthesis of ficellomycin. Biochemical characterization, crystal structure, and site-specific mutagenesis rationalize the catalytic mechanism of the unusual oxidase heterotetramer. PubMed: 37043819DOI: 10.1021/jacs.2c12507 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.29 Å) |
Structure validation
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