Jump to main content
Jump to site search


Catalytic Promiscuity of Non-native FPP Substrate in TEAS enzyme: Nonnegligible Flexibility of the Carbocation Intermediate

Abstract

The TEAS, one of the sesquiterpene cyclases (FPPC), shows enzyme promiscuity that can effectively catalyze both the natural substrate (trans,trans)-FPP and the non-native (cis,trans)-FPP substrate to generate diverse products/byproducts. So far, the catalytic mechanism of the promiscuous substrate is still unclear. In this work, QM(DFT)/MM MD simulations were employed to illuminate the predominant 1,6-closure pathway reaction mechanism for the non-native substrate (cis,trans)-FPP, while 1,10-closure pathway is the major reaction for native substrate. It has been revealed that the catalytic promiscuity of TEAS is mostly attributable to its notable conformational dynamics of the branching intermediate bisabolyl cation. The comparative studies to FSTS (another widely studied FPPC) further indicate that the intrinsic intermediate flexibility in TEAS is highly correlated to the plasticity of the enzyme active site pocket contour. Finally, we have proposed a general picture for controlling the promiscuity and fidelity in FPPC catalysis, including substrate folding, intermediate flexibility and key residues.

Back to tab navigation

Supplementary files

Publication details

The article was received on 10 Apr 2018, accepted on 08 May 2018 and first published on 08 May 2018


Article type: Paper
DOI: 10.1039/C8CP02262C
Citation: Phys. Chem. Chem. Phys., 2018, Accepted Manuscript
  •   Request permissions

    Catalytic Promiscuity of Non-native FPP Substrate in TEAS enzyme: Nonnegligible Flexibility of the Carbocation Intermediate

    R. Wu, F. Zhang, Y. Wang and X. Tang, Phys. Chem. Chem. Phys., 2018, Accepted Manuscript , DOI: 10.1039/C8CP02262C

Search articles by author

Spotlight

Advertisements