The oleate hydratase from Elizabethkingia meningoseptica (Em‐OAH) catalyzes the hydration of oleic acid (C18) to (R)‐10‐hydroxystearic acid. In previous work, low activity of Em‐OAH towards chemically synthesized (Z)‐undec‐9‐enoic acid (C11) was observed. Product formation in the hydration of the truncated C11 substrate was improved by optimizing the reaction conditions by applying statistical experiment design. Optimized reaction conditions resulted in a 2.8‐fold increase in product formation in just one quarter of the time (64 % conversion in 28 h). The applicability has been assessed in the upscaling of the conversion of (Z)‐undec‐9‐enoic acid to (S)‐10‐hydroxyundecanoic acid (132 mg product, >95 % purity). Reaction conditions developed for the hydration of C11 facilitated the first hydration of non‐natural alkenes. By using a fatty acid dummy substrate, 1‐decene was successfully hydrated to (S)‐2‐decanol with excellent stereoselectivity and 50 % conversion after four days of incubation.
The direct enantioselective addition of water to unactivated alkenes could simplify the synthesis of chiral alcohols and solve a long‐standing challenge in catalysis. Here we report that an engineered fatty acid hydratase can catalyze the asymmetric hydration of various terminal and internal alkenes. In the presence of a carboxylic acid decoy molecule for activation of the oleate hydratase from
E. meningoseptica
, asymmetric hydration of unactivated alkenes was achieved with up to 93 % conversion, excellent selectivity (>99 %
ee
, >95 % regioselectivity), and on a preparative scale.
The direct enantioselective addition of water to unactivated alkenes could simplify the synthesis of chiral alcohols and solve a long‐standing challenge in catalysis. Here we report that an engineered fatty acid hydratase can catalyze the asymmetric hydration of various terminal and internal alkenes. In the presence of a carboxylic acid decoy molecule for activation of the oleate hydratase from E. meningoseptica, asymmetric hydration of unactivated alkenes was achieved with up to 93 % conversion, excellent selectivity (>99 % ee, >95 % regioselectivity), and on a preparative scale.
The Cover shows the hydration of 1‐decene by oleate hydratase from Elizabethkingia meningoseptica in E. coli whole cells (depicted as a dark red “car”).In their Full Paper, R. M. Demming et al. demonstrate a great increase of enzymatic productivity for the conversion of short‐chain non‐natural substrates by optimizing whole cell biotransformations adding glucose, NADH and FAD as well as applying higher temperatures. The usage of the short‐chain fatty acid dummy substrate hexanoic acid drives the hydration of the “gasoline” 1‐decene resulting in the stereoselective formation of “green” (S)‐2‐decanol. With the alkene bound in the alkyl part of the V‐shaped binding pocket the reaction proceeds via a secondary carbocation followed by the nucleophilic attack of an activated water molecule.
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