Purification and Biochemical Characterization of Taxadiene Synthase from Bacillus koreensis and Stenotrophomonas maltophilia [PDF]
Scientia Pharmaceutica, 2021 Taxadiene synthase (TDS) is the rate-limiting enzyme of Taxol biosynthesis that cyclizes the geranylgeranyl pyrophosphate into taxadiene. Attenuating Taxol productivity by fungi is the main challenge impeding its industrial application; it is possible ...
Ashraf S. A. El-Sayed +7 more
doaj +4 more sources
Insights into taxadiene synthase catalysis and promiscuity facilitated by mutability landscape and molecular dynamics. [PDF]
PlantaAbstract Main conclusion Protein modeling, carbocation docking, and molecular dynamics along with structure-based mutability landscapes provided insight into taxadiene synthase catalysis (first step of the anticancer Taxol biosynthesis), protein structure–function correlations, and promiscuity.
He S +3 more
europepmc +5 more sources
Enhanced production of taxadiene in Saccharomyces cerevisiae [PDF]
Microbial Cell Factories, 2020 Background Cost-effective production of the highly effective anti-cancer drug, paclitaxel (Taxol®), remains limited despite growing global demands. Low yields of the critical taxadiene precursor remains a key bottleneck in microbial production.
Behnaz Nowrouzi +10 more
doaj +5 more sources
Sobralene, a new sex-aggregation pheromone and likely shunt metabolite of the taxadiene synthase cascade, produced by a member of the sand fly Lutzomyia longipalpis species complex. [PDF]
Tetrahedron Lett, 2018 A new sex-aggregation pheromone, sobralene, produced by the sand fly Lutzomyia longipalpis from Sobral (Ceará State, Brazil) is shown to have the novel 6,12-membered ring-fused diterpene structure 3. It is proposed that sobralene is a likely shunt metabolite of the taxadiene synthase-catalysed cyclisation of geranygeranyl diphosphate.
Palframan MJ +4 more
europepmc +8 more sources
Biosynthesis of Taxadiene in Saccharomyces cerevisiae : selection of geranylgeranyl diphosphate synthase directed by a computer-aided docking strategy. [PDF]
PLoS ONE, 2014 Identification of efficient key enzymes in biosynthesis pathway and optimization of the fitness between functional modules and chassis are important for improving the production of target compounds.
Ming-Zhu Ding +6 more
doaj +4 more sources
Metabolic Engineering of Bacillus subtilis Toward Taxadiene Biosynthesis as the First Committed Step for Taxol Production [PDF]
Frontiers in Microbiology, 2019 Terpenoids are natural products known for their medicinal and commercial applications. Metabolic engineering of microbial hosts for the production of valuable compounds, such as artemisinin and Taxol, has gained vast interest in the last few decades. The
Ingy I. Abdallah +5 more
doaj +3 more sources
Biochemistry, 2018 Taxadiene synthase (TXS) catalyzes the formation of natural product taxa-4(5),11(12)-diene (henceforth taxadiene). Taxadiene is the precursor in the formation of Taxol, which is an important natural anticancer agent. In the current study, we present a detailed mechanistic view of the biosynthesis of taxadiene by TXS using a hybrid quantum mechanics ...
Tamar Ansbacher +2 more
openaire +3 more sources
On the Role of Hydrogen Migrations in the Taxadiene System. [PDF]
Angew Chem Int Ed EnglLong range proton migrations are known to play a role in the biosynthesis of taxa‐4,11‐diene. This study demonstrates the involvement of long distance hydrogen transfers also in the mass spectrometric fragmentation, and combined approaches through site‐directed mutagenesis and enzymatic conversion of designed substrate analogs give detailed insights ...
Li H, Goldfuss B, Dickschat JS.
europepmc +2 more sources
Computational analysis of the taxadiene synthase reaction pathway
The taxadiene synthase reaction pathway defines a complex carbocation cascade that offers multiple stable intermediates that, in turn, can lead to multiple relevant products in chemistry. Because of the promiscuity of the terpene chemistry, simple modifications to the natural taxadiene synthase protein can completely modify the potential energy landscape,
Amory, Ross
core +6 more sources
ACS Synthetic Biology, 2016 Attempts at microbial production of the chemotherapeutic agent Taxol (paclitaxel) have met with limited success, due largely to a pathway bottleneck resulting from poor product selectivity of the first hydroxylation step, catalyzed by taxadien-5a-hydroxylase (CYP725A4).
Steven, Edgar +4 more
openaire +3 more sources