Carvalho Alexandra T P, Dourado Daniel F A R, Skvortsov Timofey, de Abreu Miguel, Ferguson Lyndsey J, Quinn Derek J, Moody Thomas S, Huang Meilan
School of Chemistry and Chemical Engineering, Queen's University, David Keir Building, Stranmillis Road, Belfast BT9 5AG, Northern Ireland, UK.
Phys Chem Chem Phys. 2017 Oct 11;19(39):26851-26861. doi: 10.1039/c7cp03640j.
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.
苯丙酮单加氧酶（PAMO）是拜耳-维利格单加氧酶家族中最稳定且耐热的成员，因此它是合成工业相关化合物的理想候选者。然而，其有限的底物范围在很大程度上限制了它的工业应用。在本研究中，我们首次利用分子动力学模拟、量子力学以及量子力学/分子力学计算，揭示了PAMO对天然底物苯丙酮以及线性非天然底物2-辛酮的催化机制。我们为该酶对天然芳香族底物相较于非天然线性底物的偏好性提供了理论依据。我们的研究提供了基本的原子水平见解，可用于对PAMO进行合理改造，以在工业生物催化中广泛应用，特别是在将长链脂肪油转化为潜在生物柴油的生物转化过程中。
