2y08

Structure of the substrate-free FAD-dependent tirandamycin oxidase TamLStructure of the substrate-free FAD-dependent tirandamycin oxidase TamL

Structural highlights

2y08 is a 2 chain structure with sequence from Streptomyces sp. 307-9. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.7Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

D3Y1I2_9ACTN

Publication Abstract from PubMed

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.

Tirandamycin biosynthesis is mediated by co-dependent oxidative enzymes.,Carlson JC, Li S, Gunatilleke SS, Anzai Y, Burr DA, Podust LM, Sherman DH Nat Chem. 2011 Jul 17;3(8):628-33. doi: 10.1038/nchem.1087. PMID:21778983^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Carlson JC, Li S, Gunatilleke SS, Anzai Y, Burr DA, Podust LM, Sherman DH. Tirandamycin biosynthesis is mediated by co-dependent oxidative enzymes. Nat Chem. 2011 Jul 17;3(8):628-33. doi: 10.1038/nchem.1087. PMID:21778983 doi:10.1038/nchem.1087

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OCA

[1] Carlson JC, Li S, Gunatilleke SS, Anzai Y, Burr DA, Podust LM, Sherman DH. Tirandamycin biosynthesis is mediated by co-dependent oxidative enzymes. Nat Chem. 2011 Jul 17;3(8):628-33. doi: 10.1038/nchem.1087. PMID:21778983 doi:10.1038/nchem.1087

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