2Y3S

Structure of the tirandamycine-bound FAD-dependent tirandamycin oxidase TamL in C2 space group

Summary for 2Y3S

• Entry DOI: 10.2210/pdb2y3s/pdb
• Related: 2Y08 2Y3R 2Y4G
• Descriptor: TAML, FLAVIN-ADENINE DINUCLEOTIDE, TIRANDAMYCIN E, ... (7 entities in total)
• Functional Keywords: oxidoreductase
• Biological source: STREPTOMYCES SP. 307-9
• Total number of polymer chains: 2
• Total formula weight: 119443.81

Authors

Carlson, J.C.,Li, S.,Gunatilleke, S.S.,Anzai, Y.,Burr, D.A.,Podust, L.M.,Sherman, D.H. (deposition date: 2010-12-23, release date: 2011-06-29, Last modification date: 2024-10-09)

Primary citation

Carlson, J.C.,Li, S.,Gunatilleke, S.S.,Anzai, Y.,Burr, D.A.,Podust, L.M.,Sherman, D.H.
Tirandamycin Biosynthesis is Mediated by Co-Dependent Oxidative Enzymes
Nat.Chem, 3:628-, 2011

PubMed Abstract: Elucidation of natural product biosynthetic pathways provides important insights into the assembly of potent bioactive molecules, and expands access to unique enzymes able to selectively modify complex substrates. Here, we show full reconstitution, in vitro, of an unusual multi-step oxidative cascade for post-assembly-line tailoring of tirandamycin antibiotics. This pathway involves a remarkably versatile and iterative cytochrome P450 monooxygenase (TamI) and a flavin adenine dinucleotide-dependent oxidase (TamL), which act co-dependently through the repeated exchange of substrates. TamI hydroxylates tirandamycin C (TirC) to generate tirandamycin E (TirE), a previously unidentified tirandamycin intermediate. TirE is subsequently oxidized by TamL, giving rise to the ketone of tirandamycin D (TirD), after which a unique exchange back to TamI enables successive epoxidation and hydroxylation to afford, respectively, the final products tirandamycin A (TirA) and tirandamycin B (TirB). Ligand-free, substrate- and product-bound crystal structures of bicovalently flavinylated TamL oxidase reveal a likely mechanism for the C10 oxidation of TirE.

PubMed: 21778983
DOI: 10.1038/NCHEM.1087

Experimental method

X-RAY DIFFRACTION (1.67 Å)