Metal-dependent enzyme symmetry guides the biosynthetic flux of terpene precursors.

Terpenoids account for more than 60% of all natural products, and their carbon skeletons originate from common isoprenoid units of different lengths such as geranyl pyrophosphate and farnesyl pyrophosphate. Here we characterize a metal-dependent, bifunctional isoprenyl diphosphate synthase from the leaf beetle Phaedon cochleariae by structural and functional analyses. Inter- and intramolecular cooperative effects in the homodimer strongly depend on the provided metal ions and regulate the biosynthetic flux of terpene precursors to either biological defence or physiological development.

Correction: Block et al. Fluorinated Analogs of Organosulfur Compounds from Garlic (): Synthesis, Chemistry and Anti-Angiogenesis and Antithrombotic Studies. 2017, , 2081.

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Enhanced structural diversity in terpenoid biosynthesis: enzymes, substrates and cofactors.

The enormous diversity of terpenes found in nature is generated by enzymes known as terpene synthases, or cyclases. Some are also known for their ability to convert a single substrate into multiple products. This review comprises monoterpene and sesquiterpene synthases that are multiproduct in nature along with the regulation factors that can alter the product specificity of multiproduct terpene synthases without genetic mutations.

Fluorinated Analog NMR s of Organosulfur Compounds from Garlic (Allium sativum): Synthesis, Chemistry and Anti-Angiogenesis and Antithrombotic Studies.

We describe the synthesis, reactivity, and antithrombotic and anti-angiogenesis activity of difluoroallicin (-(2-fluoroallyl) 2-fluoroprop-2-ene-1-sulfinothioate) and -2-fluoro-2-propenyl-l-cysteine, both easily prepared from commercially available 3-chloro-2-fluoroprop-1-ene, as well as the synthesis of 1,2-bis(2-fluoroallyl)disulfane, 5-fluoro-3-(1-fluorovinyl)-3,4-dihydro-1,2-dithiin, trifluoroajoene ((,)-1-(2-fluoro-3-((2-fluoroallyl)sulfinyl)prop-1-en-1-yl)-2-(2-fluoroallyl)disulfane), and a bis(2-fluoroallyl)polysulfane mixture. All tested organosulfur compounds demonstrated effective inhibition of either FGF or VEG-mediated angiogenesis (anti-angiogenesis activity) in the chick chorioallantoic membrane (CAM) or the mouse Matrigel models. No embryo mortality was observed.

Alternate Cyclization Cascade Initiated by Substrate Isomer in Multiproduct Terpene Synthase from Medicago truncatula.

Promiscuity of terpene synthases results in the enormous diversity of terpenes found in nature. Multiproduct sesquiterpene synthase MtTPS5 isolated from Medicago truncatula generates 27 optically pure products from its natural substrate (2E,6E)-farnesyl diphosphate (FDP). In order to study the promiscuity of MtTPS5, (2Z,6E)-FDP, an analogue of presumptive reaction intermediates from natural reaction cascade, was utilized as a substrate.

Trifluoroselenomethionine: A New Unnatural Amino Acid.

Trifluoroselenomethionine (TFSeM), a new unnatural amino acid, was synthesized in seven steps from N-(tert-butoxycarbonyl)-l-aspartic acid tert-butyl ester. TFSeM shows enhanced methioninase-induced cytotoxicity, relative to selenomethionine (SeM), toward HCT-116 cells derived from human colon cancer. Mechanistic explanations for this enhanced activity are computationally and experimentally examined.

Substrate geometry controls the cyclization cascade in multiproduct terpene synthases from Zea mays.

Multiproduct terpene synthases TPS4-B73 and TPS5-Delprim from maize (Zea mays) catalyze the conversion of farnesyl diphosphate (FDP) and geranyl diphosphate (GDP) into a complex mixture of sesquiterpenes and monoterpenes, respectively. Various isotopic and geometric isomers of natural substrates like (2Z)-[2-(2)H]- and [2,4,4,9,9,9-(2)H6]-(GDP) and (2Z,6E)-[2-(2)H]- and [2,4,4,13,13,13-(2)H6]-(FDP) were synthesized analogous to presumptive reaction intermediates. On incubation with labeled (2Z) substrates, TPS4 and TPS5 showed much lower kinetic isotope effects than the labeled (2E) substrates.

Inhibition of a multiproduct terpene synthase from Medicago truncatula by 3-bromoprenyl diphosphates.

The multiproduct sesquiterpene synthase MtTPS5 from Medicago truncatula catalyzes the conversion of farnesyl diphosphate (FDP) into a complex mixture of 27 terpenoids. 3-Bromo substrate analogues of geranyl diphosphate (3-BrGDP) and farnesyl diphosphate (3-BrFDP) were evaluated as substrates of MTPS5 enzyme. Kinetic studies demonstrated that these compounds were highly potent competitive inhibitors of the MtTPS5 enzyme with fast binding and slow reversibility.

Isotope sensitive branching and kinetic isotope effects to analyse multiproduct terpenoid synthases from Zea mays.

Multiproduct terpene synthases TPS4-B73 and TPS5-Delprim from Zea mays exhibit isotopically sensitive branching in the formation of mono- and sesquiterpene volatiles. The impact of the kinetic isotope effects and the stabilization of the reactive intermediates by hyperconjugation along with the shift of products from alkenes to alcohols are discussed.

Applications of direct analysis in real time-mass spectrometry (DART-MS) in Allium chemistry. (Z)-butanethial S-oxide and 1-butenyl thiosulfinates and their S-(E)-1-butenylcysteine S-oxide precursor from Allium siculum.

Lachrymatory (Z)-butanethial S-oxide along with several 1-butenyl thiosulfinates was detected by DART mass spectrometry upon cutting Allium siculum , a popular ornamental Allium species used in some cultures as a spice. (Z)-Butanethial S-oxide isolated from the plant was shown to be identical to a synthetic sample. Its likely precursor, (R(S),R(C),E)-S-(1-butenyl)cysteine S-oxide (homoisoalliin), was isolated from homogenates of A.