Journal Article

FZJ-2016-06532

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png One-Pot, Two-Step Hydroxylation of the Macrocyclic Diterpenoid β-Cembrenediol Catalyzed by P450 BM3 Mutants

Le-Huu, P. ; Petrović, D.FZJ* ; Strodel, B.FZJ* ; Urlacher, V. B. (Corresponding author)

2016
WILEY-VCH Verlag Weinheim

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Please use a persistent id in citations: doi:10.1002/cctc.201600973

Abstract: Cytochrome P450 monooxygenases (P450s) are involved in the biosynthesis of a wide range of bioactive secondary metabolites. They often introduce several oxy functionalities at different positions of a substrate through multiple steps and produce a range of oxidized derivatives. Herein, we describe a one-pot two-step hydroxylation of the diterpenoid b-cembrenediol isolated from the plant Nicotiana tabacum. This 14-membered macrocycle shows neuroprotective effects and is, along with its oxidized derivatives, of pharmaceutical interest. Sequential hydroxylations catalyzed by the regioselective P450 BM3 mutants F87A/I263L and V78A/F87G yielded the epimeric (9S,10R/S)-b-cembrenetetraols with a diastereomeric ratio of 48:52. The replacement of the mutant V78A/F87G with L75A/ V78A/F87G in the second step improves the diastereomeric ratio up to 10:90. Absolute configurations of the newly introduced hydroxy groups were determined by quantum-mechanical calculations of NMR spectra.

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Contributing Institute(s):

1. Strukturbiochemie (ICS-6)

Research Program(s):

1. 553 - Physical Basis of Diseases (POF3-553) (POF3-553)

Appears in the scientific report 2016

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Database coverage:
; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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