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bioRxiv · 10.64898/2026.05.07.723505

Hydrophobic pocket engineering of arylmalonate decarboxylase expands its substrate scope towards the synthesis of the (R)-enantiomers of sterically hindered carboxylic acids

van der Pol, E.·Krammer, L.-M.·Eder, J.·Gross, D.·Fischer, R.·Miyamoto, K.·Breinbauer, R.·Kourist, R.
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Abstract

Arylmalonate decarboxylase (AMDase) stereoselectively converts disubstituted malonates to chiral carboxylic acids, but its substrate spectrum is very limited regarding the size of the smaller substituent. Inspired by the observation that (S)-selective AMDase variants also convert larger substrates, we unlocked the synthesis of the (R)-enantiomers of -aryl and -alkenyl n-butanoic and n-pentanoic acids, respectively, in exquisite enantiopurity.

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van der Pol, E., Krammer, L.-M., Eder, J., Gross, D., Fischer, R., Miyamoto, K., Breinbauer, R., Kourist, R.. 2026-05-08. Hydrophobic pocket engineering of arylmalonate decarboxylase expands its substrate scope towards the synthesis of the (R)-enantiomers of sterically hindered carboxylic acids. https://doi.org/10.64898/2026.05.07.723505

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