10219-75-7Relevant academic research and scientific papers
Mechanism-Based Post-Translational Modification and Inactivation in Terpene Synthases
Kersten, Roland D.,Diedrich, Jolene K.,Yates, John R.,Noel, Joseph P.
, p. 2501 - 2511 (2015)
Terpenes are ubiquitous natural chemicals with diverse biological functions spanning all three domains of life. In specialized metabolism, the active sites of terpene synthases (TPSs) evolve in shape and reactivity to direct the biosynthesis of a myriad of chemotypes for organismal fitness. As most terpene biosynthesis mechanistically involves highly reactive carbocationic intermediates, the protein surfaces catalyzing these cascade reactions possess reactive regions possibly prone to premature carbocation capture and potentially enzyme inactivation. Here, we show using proteomic and X-ray crystallographic analyses that cationic intermediates undergo capture by conserved active site residues leading to inhibitory self-alkylation. Moreover, the level of cation-mediated inactivation increases with mutation of the active site, upon changes in the size and structure of isoprenoid diphosphate substrates, and alongside increases in reaction temperatures. TPSs that individually synthesize multiple products are less prone to self-alkylation then TPSs possessing relatively high product specificity. In total, the results presented suggest that mechanism-based alkylation represents an overlooked mechanistic pressure during the evolution of cation-derived terpene biosynthesis.
Biotransformation of aristolane- and 2,3-secoaromadendrane-type sesquiterpenoids having a 1,1-dimethylcyclopropane ring by Chlorella fusca var. vacuolata, Mucor species, and Aspergillus niger
Furusawa, Mai,Hashimoto, Toshihiro,Noma, Yoshiaki,Asakawa, Yoshinori
, p. 861 - 868 (2007/10/03)
Biotransformation of the aristolane-type sesquiterpene hydrocarbon (+)-1(10)-aristolene (1) from the crude drug Nardostachys chinensis and of the 2,3-secoaromadendrane-type sesquiterpene lactone plagiochilide (2) from the liverwort Plagiochila fruticosa by three microorganisms, Chlorella fusca var. vacuolata, Mucor species, and Aspergillus niger was investigated. C. fusca var. vacuolata and Mucor sp. introduced oxygen function into the cyclohexane ring of aristolene while A. niger oxidized stereoselectively one methyl of the 1,1-dimethyl group on the cyclopropane ring of aristolanes and 2,3-secoaromadendrane to give C-12 primary alcohol and C-12 carboxylic acid. The possible metabolic pathway of the formation of new metabolites is discussed. The stereostructures of new metabolites were established by a combination of NMR spectroscopy including HMBC and NOESY, X-ray crystallographic analysis, and chemical reaction.
