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Issue 13, 2006
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Stabilisation of transition states prior to and following eudesmane cation in aristolochene synthase

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Abstract

The mechanistic details of the cyclisation of farnesylpyrophosphate (FPP) by aristolochene synthase (AS) from Penicillium roqueforti have only recently begun to emerge, mainly through the analysis of the reaction products generated by AS-mutants. The reaction proceeds through several intermediates including germacrene A and eudesmane cation. Previous work suggested that the side chain of phenylalanine 178 promoted the conversion of eudesmane cation to aristolochene. We now report that the catalytic function of this residue during the conversion of eudesmane cation to aristolochene is mainly due to the large size of its side chain, which facilitates the hydride shift from C2 to C3, rather than its aromatic character. In addition, F178 appears to control the regioselectivity of the final deprotonation step and, together with F112, helps stabilise the developing positive charge on C1 after the expulsion of pyrophosphate from the substrate. These results complete a screen of likely active-site aromatic residues and establish their respective roles in the conversion of FPP to aristolochene.

Graphical abstract: Stabilisation of transition states prior to and following eudesmane cation in aristolochene synthase

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Publication details

The article was received on 21 Mar 2006, accepted on 08 May 2006 and first published on 25 May 2006


Article type: Paper
DOI: 10.1039/B604147G
Citation: Org. Biomol. Chem., 2006,4, 2563-2567

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    Stabilisation of transition states prior to and following eudesmane cation in aristolochene synthase

    S. Forcat and R. K. Allemann, Org. Biomol. Chem., 2006, 4, 2563
    DOI: 10.1039/B604147G

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