Interplay between two spin states determines the hydroxylation catalyzed by P450 monooxygenase from Trichoderma brevicompactum

J Comput Chem. 2020 May 30;41(14):1330-1336. doi: 10.1002/jcc.26177. Epub 2020 Feb 17.


Tri11 (now renamed as tri22) encoded cytochrome P450 monooxygenase in Trichoderma brevicompactum catalyzes the C-4 C-H hydroxylation of 12, 13-epoxytrichothec-9-ene (EPT) to produce trichodermol in the biosynthetic pathway of trichodermin/harzianum A. The density functional theory (DFT)-quantum mechanics (QM) approach is applied to elucidate the hydroxylation of EPT by using a model active species of P450 (Cpd I). The QM calculations were performed on the active site complex, to find out transition-state structure, intermediate, and product complexes for the two spin states at different potential energy surfaces. The two state reactivity rebound-free product formation resulted from the interplay of two spin states (doublet and quartet).

Keywords: Trichoderma brevicompactum; cytochrome P450 monooxygenase; density functional theory; high spin state; low spin state.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocatalysis
  • Cytochrome P-450 Enzyme System / chemistry
  • Cytochrome P-450 Enzyme System / metabolism*
  • Density Functional Theory
  • Hydroxylation
  • Hypocreales / enzymology*
  • Trichodermin / chemistry
  • Trichodermin / metabolism*
  • Trichothecenes / chemistry
  • Trichothecenes / metabolism*


  • Trichothecenes
  • 12,13-epoxytrichothec-9-ene
  • Trichodermin
  • Cytochrome P-450 Enzyme System

Supplementary concepts

  • Trichoderma brevicompactum