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The last step in cephalosporin C formation revealed: Crystal Structures of Deacetylcephalosporin C Acetyltransferase from Acremonium chrysogenum in Complexes with Reaction Intermediates
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics. (Hajdu)
2008 (English)In: Journal of Molecular Biology, ISSN 0022-2836, E-ISSN 1089-8638, Vol. 377, no 3, p. 935-944Article in journal (Refereed) Published
Abstract [en]

Deacetylcephalosporin C acetyltransferase (DAC-AT) catalyses the last step in the biosynthesis of cephalosporin C, a broad-spectrum beta-lactam antibiotic of large clinical importance. The acetyl transfer step has been suggested to be limiting for cephalosporin C biosynthesis, but has so far escaped detailed structural analysis. We present here the crystal structures of DAC-AT in complexes with reaction intermediates, providing crystallographic snapshots of the reaction mechanism. The enzyme is found to belong to the alpha/beta hydrolase class of acetyltransferases, and the structures support previous observations of a double displacement mechanism for the acetyl transfer reaction in other members of this class of enzymes. The structures of DAC-AT reported here provide evidence of a stable acyl - enzyme complex, thus underpinning a mechanism involving acetylation of a catalytic serine residue by acetyl coenzyme A, followed by transfer of the acetyl group to deacetylcephalosporin C through a suggested tetrahedral transition state.

Place, publisher, year, edition, pages
2008. Vol. 377, no 3, p. 935-944
Keywords [en]
cephalosporin C, beta-lactam antibiotic biosynthesis, Acremonium chrysogenum, X-ray crystallography, acetyl transferase
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-287545OAI: oai:DiVA.org:uu-287545DiVA, id: diva2:922905
Available from: 2016-04-25 Created: 2016-04-25 Last updated: 2017-11-30

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