Catalytic mechanism of Phenylacetone monooxygenases for non-native linear substrates: implications on rational engineering of BVMOs to expand the substrate specificity

Alexandra T. P. Carvalho, Daniel F. A. R. Dourado, Timofey Skvortsov, Miguel de Abreu, Lyndsey Ferguson, Derek J. Quinn, Thomas S. Moody, Meilan Huang*

*Corresponding author for this work

Research output: Contribution to journalArticle

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Phenylacetone monooxygenase (PAMO) is the most stable and thermo-tolerant member of the Baeyer-Villiger monooxygenase family, and therefore it is an ideal candidate for the synthesis of industrially relevant compounds. However, its limited substrate scope has largely limited its industrial applications. In the present work, we provide, for the first time, the catalytic mechanism of PAMO for the native substrate phenylacetone as well as for a linear non-native substrate 2-octanone, using molecular dynamics simulations, quantum mechanics and quantum mechanics/molecular mechanics calculations. We provide a theoretical basis for the preference of the enzyme for the native aromatic substrate over non-native linear substrates. Our study provides fundamental atomic-level insights that can be employed in the rational engineering of PAMO for wide applications in industrial biocatalysis, in particular, in the biotransformation of long-chain aliphatic oils into potential biodiesels.

Original languageEnglish
Pages (from-to)26851-26861
Number of pages11
JournalPhysical Chemistry Chemical Physics
Issue number39
Early online date07 Sep 2017
Publication statusEarly online date - 07 Sep 2017


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