Wang et al. recently reported an in silico study of the trichodiene synthase (TDS) conversion of farnesyl diphosphate (FPP) to trichodiene (TD) (Wang et al., 2017, , 5841-5846). Although the methods and level of theory used in that work are nearly identical to our own recent work on this system (Dixit et al., 2017, , 812-818), Wang et al. reach rather different conclusions. The authors claimed to obtain a "very credible" mechanism for the biosynthesis of TD and optimized the optimal folding mode of FPP in the 1,6-ring closure in TDS. However, the folding mode of the FPP substrate that was presented contradicts well-established NMR and mass spectrometry data. Moreover, the authors make numerous incorrect statements regarding our earlier work.
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http://dx.doi.org/10.1021/acscatal.7b02823 | DOI Listing |
Methods Enzymol
June 2024
State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, P.R. China. Electronic address:
Magnesium ions (Mg) are crucial in class II terpene cyclases that utilize substrates with diphosphate groups. Interestingly, these enzymes catalyze reactions without cleaving the diphosphate group, instead initiating the reaction through protonation. In our recent research, we discovered a novel class II sesquiterpene cyclase in Streptomyces showdoensis.
View Article and Find Full Text PDFInt J Mol Sci
May 2024
Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Cádiz, 11510 Puerto Real, Cádiz, Spain.
The genome sequencing of supplies a general overview of the map of genes involved in secondary metabolite synthesis. genomic data reveals that this phytopathogenic fungus has seven sesquiterpene cyclase () genes that encode proteins involved in the farnesyl diphosphate cyclization. Three sesquiterpene cyclases (BcStc1, BcStc5 and BcStc7) are characterized, related to the biosynthesis of botrydial, abscisic acid and (+)-4-epi-eremophilenol, respectively.
View Article and Find Full Text PDFJ Fungi (Basel)
May 2024
State Key Laboratory of Bioreactor Engineering, East China University of Science of Technology, Shanghai 200237, China.
Sesquiterpenoids served as an important source for natural product drug discovery. Although genome mining approaches have revealed numerous novel sesquiterpenoids and biosynthetic enzymes, the comprehensive landscape of fungal sesquiterpene synthases (STSs) remains elusive. In this study, 123 previously reported fungal STSs were subjected to phylogenetic analysis, resulting in the identification of a fungi-specific STS family known as trichodiene synthase-like sesquiterpene synthases (TDTSs).
View Article and Find Full Text PDFBiochemistry
March 2024
Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
The sesquiterpene cyclase -isozizaene synthase (EIZS) from catalyzes the metal-dependent conversion of farnesyl diphosphate (FPP) into the complex tricyclic product -isozizaene. This remarkable transformation is governed by an active site contour that serves as a template for catalysis, directing the conformations of multiple carbocation intermediates leading to the final product. Mutagenesis of residues defining the active site contour remolds its three-dimensional shape and reprograms the cyclization cascade to generate alternative cyclization products.
View Article and Find Full Text PDFJ Am Chem Soc
December 2022
State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, Jiangsu, China.
Terpene cyclases (TCs), extraordinary enzymes that create the structural diversity seen in terpene natural products, are traditionally divided into two classes, class I and class II. Although the structural and mechanistic features of class I TCs are well-known, the corresponding details in class II counterparts have not been fully characterized. Here, we report the genome mining discovery and structural characterization of two class II sesquiterpene cyclases (STCs) from .
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