Reply to Comment on “Substrate Folding Modes in Trichodiene Synthase: A Determinant of Chemo- and Stereoselectivity”

Abstract

Major et al. claimed that the patterns of proton transfer (Re- vs Si-face) and methyl transfer (C12 or C13) in our recent work [Wang et al. ACS Catal. 2017, 7, 5841−5846] on biocatalysis in trichodiene synthase (FSTS) contradict the so-called “well-established” spectrometric data and make “incorrect statements” on their previous work [Major et al. ACS Catal. 2017, 7, 812−818]. This response aims to clarify that the proton/methyl transfer styles are not yet validated experimentally, at least from their citations in the rebuttal paper [Major et al. DOI: 10.1021/acscatal.7b02823] and other studies we have found. Furthermore, the main conclusion (we proposed a general rule) in our previous work indeed is not dependent on those two reaction steps. In addition, we also compare the different views on reaction energetics, chemo-selectivity, and theoretical modeling for FSTS between Major’s and our work, which can serve as a framework for citation by other research groups and academic discussion in the future.