Crystal structure determination of aristolochene synthase from the blue cheese mold, Penicillium roqueforti

The 2.5-Angstrom resolution crystal structure of recombinant aristolochene synthase from the blue cheese mold, Penicillium roqueforti, is the first of a fungal terpenoid cyclase, The structure of the enzyme reveals active sit e features that participate in the cyclization of the universal sesquiterpe ne cyclase substrate, farnesyl diphosphate, to form the bicyclic hydrocarbo n aristolochene. Metal-triggered carbocation formation initiates the cycliz ation cascade, which proceeds through multiple complex intermediates to yie ld one exclusive structural and stereochemical isomer of aristolochene, Str uctural homology of this fungal cyclase with plant and bacterial terpenoid cyclases, despite minimal amino acid sequence identity, suggests divergence from a common, primordial ancestor in the evolution of terpene biosynthesi s.