To resolve the issue, we applied herein MD simulations followed by QM/MM calculations, for WT P450OleT and P450BSβ. These calculations lead to a revised mechanism through which OleT performs decarboxylation of fatty acids, due to the assistance of a protonated His85. This residue creates a local electric field (LEF), which is larger than the one created by Q85 and ultimately dictates the product selectivities of P450OleT vs. P450BSβ.