A Single Residue Change Leads to a Hydroxylated Product from the Class II Diterpene Cyclization Catalyzed by Abietadiene Synthase

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2012-01-01
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Criswell, Jared
Potter, Kevin
Shephard, Freya
Beale, Michael
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Class II diterpene cyclases catalyze bicyclization of geranylgeranyl diphosphate. While this reaction typically is terminated via methyl deprotonation to yield copalyl diphosphate, in rare cases hydroxylated bicycles are produced instead. Abietadiene synthase is a bifunctional diterpene cyclase that usually produces a copalyl diphosphate intermediate. Here it is shown that substitution of aspartate for a conserved histidine in the class II active site of abietadiene synthase leads to selective production of 8α-hydroxy-CPP instead, demonstrating striking plasticity.

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Reprinted (adapted) with permission from Organic Letters 14 (2012): 5828, doi:10.1021/ol3026022. Copyright 2012 American Chemical Society.

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Sun Jan 01 00:00:00 UTC 2012
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