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  QM/MM study of the taxadiene synthase mechanism

van Rijn, J., Escorcia Cabrera, A. M., & Thiel, W. (2019). QM/MM study of the taxadiene synthase mechanism. Journal of Computational Chemistry, 40(21), 1902-1910. doi:10.1002/jcc.25846.

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jcc25846-sup-0001-supinfo_pub 631.pdf (Supplementary material), 2MB
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 Creators:
van Rijn, Jeaphianne1, Author           
Escorcia Cabrera, Andrés Mauricio1, Author           
Thiel, Walter1, Author           
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1Research Department Thiel, Max-Planck-Institut für Kohlenforschung, Max Planck Society, ou_1445590              

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Free keywords: enzyme catalysis; enzyme promiscuity; QM/MM; terpene synthase; taxadiene
 Abstract: Combined quantum mechanics/molecular mechanics (QM/MM) calculations were used to investigate the reaction mechanism of taxadiene synthase (TXS). TXS catalyzes the cyclization of geranylgeranyl diphosphate (GGPP) to taxadiene (T) and four minor cyclic products. All these products originate from the deprotonation of carbocation intermediates. The reaction profiles for the conversion of GGPP to T as well as to minor products were calculated for different configurations of relevant TXS carbocation complexes. The QM region was treated at the M06‐2X/TZVP level, while the CHARMM27 force field was used to describe the MM region. The QM/MM calculations suggest a reaction pathway for the conversion of GGPP to T, which slightly differs from previous proposals regarding the number of reaction steps and the conformation of the carbocations. The QM/MM results also indicate that the formation of minor products via water‐assisted deprotonation of the carbocations is highly exothermic, by about −7 to −23 kcal/mol. Curiously, however, the computed barriers and reaction energies indicate that the formation of some of the minor products is more facile than the formation of T. Thus, the present QM/MM calculations provide detailed insights into possible reaction pathways and into the origin of the promiscuity of TXS, but they do not reproduce the product distribution observed experimentally.

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Language(s): eng - English
 Dates: 2019-02-172019-04-152019-05-062019-08-05
 Publication Status: Published in print
 Pages: 9
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1002/jcc.25846
 Degree: -

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Title: Journal of Computational Chemistry
  Abbreviation : J. Comput. Chem.
Source Genre: Journal
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Publ. Info: New York : Wiley
Pages: - Volume / Issue: 40 (21) Sequence Number: - Start / End Page: 1902 - 1910 Identifier: ISSN: 0192-8651
CoNE: https://pure.mpg.de/cone/journals/resource/954925489848