6YQ0
Promiscuous Reductase LugOII Catalyzes Keto-reduction at C1 during Lugdunomycin Biosynthesis
This is a non-PDB format compatible entry.
Summary for 6YQ0
| Entry DOI | 10.2210/pdb6yq0/pdb |
| Descriptor | Monooxygenase, 1,2-ETHANEDIOL, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (5 entities in total) |
| Functional Keywords | lugdunomycin, keto-reduction, short chain alcohol reductase, rossmann fold, antibiotic |
| Biological source | Streptomyces sp. QL37 |
| Total number of polymer chains | 2 |
| Total formula weight | 56622.93 |
| Authors | Xiao, X.,Elsayed, S.S.,Wu, C.,van der Heul, H.,Prota, A.,Huang, J.,Guo, R.,Abrahams, J.P.,van Wezel, G.P. (deposition date: 2020-04-16, release date: 2020-09-16, Last modification date: 2024-01-24) |
| Primary citation | Xiao, X.,Elsayed, S.S.,Wu, C.,van der Heul, H.U.,Metsa-Ketela, M.,Du, C.,Prota, A.E.,Chen, C.C.,Liu, W.,Guo, R.T.,Abrahams, J.P.,van Wezel, G.P. Functional and Structural Insights into a Novel Promiscuous Ketoreductase of the Lugdunomycin Biosynthetic Pathway. Acs Chem.Biol., 15:2529-2538, 2020 Cited by PubMed Abstract: Angucyclines are a structurally diverse class of actinobacterial natural products defined by their varied polycyclic ring systems, which display a wide range of biological activities. We recently discovered lugdunomycin (), a highly rearranged polyketide antibiotic derived from the angucycline backbone that is synthesized via several yet unexplained enzymatic reactions. Here, we show via , , and structural analysis that the promiscuous reductase LugOII catalyzes both a C6 and an unprecedented C1 ketoreduction. This then sets the stage for the subsequent C-ring cleavage that is key to the rearranged scaffolds of . The 1.1 Å structures of LugOII in complex with either ligand 8--Methylrabelomycin () or 8--Methyltetrangomycin () and of apoenzyme were resolved, which revealed a canonical Rossman fold and a remarkable conformational change during substrate capture and release. Mutational analysis uncovered key residues for substrate access, position, and catalysis as well as specific determinants that control its dual functionality. The insights obtained in this work hold promise for the discovery and engineering of other promiscuous reductases that may be harnessed for the generation of novel biocatalysts for chemoenzymatic applications. PubMed: 32840360DOI: 10.1021/acschembio.0c00564 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.08 Å) |
Structure validation
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