alpha-farnesene and beta-farnesene

Isoprenoids have been identified and used as natural pharmaceuticals, fragrances, solvents, and, more recently, advanced biofuels. Although isoprenoids are most commonly found in plants, researchers have successfully engineered both the eukaryotic and prokaryotic isoprenoid biosynthetic pathways to produce these valuable chemicals in microorganisms at high yields. The microbial synthesis of the precursor to artemisinin--an important antimalarial drug produced from the sweet wormwood Artemisia annua--serves as perhaps the most successful example of this approach. Through advances in synthetic biology and metabolic engineering, microbial-derived semisynthetic artemisinin may soon replace plant-derived artemisinin as the primary source of this valuable pharmaceutical. The richness and diversity of isoprenoid structures also make them ideal candidates for advanced biofuels that may act as "drop-in" replacements for gasoline, diesel, and jet fuel. Indeed, the sesquiterpenes farnesene and bisabolene, monoterpenes pinene and limonene, and hemiterpenes isopentenol and isopentanol have been evaluated as fuels or fuel precursors. As in the artemisinin project, these isoprenoids have been produced microbially through synthetic biology and metabolic engineering efforts. Here, we provide a brief review of the numerous isoprenoid compounds that have found use as pharmaceuticals, flavors, commodity chemicals, and, most importantly, advanced biofuels. In each case, we highlight the metabolic engineering strategies that were used to produce these compounds successfully in microbial hosts. In addition, we present a current outlook on microbial isoprenoid production, with an eye towards the many challenges that must be addressed to achieve higher yields and industrial-scale production.

Topics: Artemisinins; Biofuels; Biological Products; Biotechnology; Chemistry, Pharmaceutical; Drug Design; Industrial Microbiology; Metabolic Engineering; Sesquiterpenes; Synthetic Biology

Farnesol, derived from farnesyl pyrophosphate in the sterols biosynthetic pathway, is a molecule with three unsaturations and four possible isomers.. The study involved the addition of exogenous. Exogenously added. The findings collectively offer the first insights into the mechanism of action of farnesol on

Topics: Candida albicans; Farnesol; Leishmania; Leishmania mexicana; Sterols

Oxidative stress is highly damaging to cellular macromolecules and is also considered a main cause of the loss and impairment of neurons in several neurodegenerative disorders. Recent reports indicate that farnesene (FNS), an acyclic sesquiterpene, has antioxidant properties. However, little is known about the effects of FNS on oxidative stress-induced neurotoxicity. We used hydrogen peroxide (H2O2) exposure for 6 h to model oxidative stress. Therefore, this experimental design allowed us to explore the neuroprotective potential of different FNS isomers (α-FNS and β-FNS) and their mixture (Mix-FNS) in H2O2-induced toxicity in newborn rat cerebral cortex cell cultures for the first time. For this aim, both MTT and lactate dehydrogenase assays were carried out to evaluate cell viability. Total antioxidant capacity (TAC) and total oxidative stress (TOS) parameters were used to assess oxidative alterations. In addition to determining of 8-hydroxy-2-deoxyguanosine (8-OH-dG) levels in vitro, the comet assay was also performed for measuring the resistance of neuronal DNA to H2O2-induced challenge. Our results showed that survival and TAC levels of the cells decreased, while TOS, 8-OH-dG levels and the mean values of the total scores of cells showing DNA damage (comet assay) increased in the group treated with H2O2 alone. But pretreatment of FNS suppressed the cytotoxicity, genotoxicity and oxidative stress, which were increased by H2O2 in clear type of isomers and applied concentration-dependent manners. The order of antioxidant effectiveness for modulating H2O2-induced oxidative stress-based neurotoxicity and genotoxicity is as β-FNS > Mix-FNS > α-FNS.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antioxidants; Cell Death; Cell Survival; Cells, Cultured; Cerebral Cortex; Deoxyguanosine; DNA Damage; Hydrogen Peroxide; L-Lactate Dehydrogenase; Neurons; Neuroprotective Agents; Neurotoxins; Oxidative Stress; Rats; Sesquiterpenes

The rate constants for the gas-phase reactions of hydroxyl radicals and ozone with the biogenic hydrocarbons β-ocimene, β-myrcene, and α- and β-farnesene were measured using the relative rate technique over the temperature ranges 313-423 (for OH) and 298-318 K (for O₃) at about 1 atm total pressure. The OH radicals were generated by photolysis of H₂O₂, and O₃ was produced from the electrolysis of O₂. Helium was used as the diluent gas. The reactants were detected by online mass spectrometry, which resulted in high time resolution, allowing large amounts of data to be collected and used in the determination of the Arrhenius parameters. The following Arrhenius expressions have been determined for these reactions (in units of cm³ molecules⁻¹ s⁻¹): for β-ocimene + OH, k = (4.35(-0.66)(+0.78)) × 10⁻¹¹ exp[(579 ± 59)/T]; for β-ocimene + O₃, k = (3.15(-0.95)(+1.36)) × 10⁻¹⁵ exp[-(626 ± 110)/T]; for β-myrcene + O₃, k = (2.21(-0.66)(+0.94)) × 10⁻¹⁵ exp[-(520 ± 109)/T]; for α-farnesene + OH, k(OH) = (2.19 ± 0.11) × 10⁻¹⁰ for 23-413 K; for α-farnesene + O₃, k = (3.52(-2.54)(+9.09)) × 10⁻¹² exp[-(2589 ± 393)/T]; for β-farnesene + OH, k(OH) = (2.88 ± 0.15) × 10⁻¹⁰ for 323-423 K; for β-farnesene + O₃, k = (1.81(-1.19)(+3.46)) × 10⁻¹² exp[-(2347 ± 329)/T]. The Arrhenius parameters here are the first to be reported. The reactions of α- and β-farnesene with OH showed no significant temperature dependence. Atmospheric residence times due to reactions with OH and O₃ were also presented.

Topics: Acyclic Monoterpenes; Alkenes; Atmosphere; Gases; Hydroxyl Radical; Kinetics; Mass Spectrometry; Monoterpenes; Ozone; Sesquiterpenes; Temperature

Using automated solid-phase dynamic extraction and gas chromatography-mass spectrometry, our search for urinary chemical signals from ovulatory female African elephants (Loxodonta africana) has revealed the bark beetle aggregation pheromones frontalin, exo-brevicomin, and endo-brevicomin, as well as their precursors and the aphid alarm pheromones (E,E)-alpha-farnesene and (E)-beta-farnesene. Enantiomeric ratios for brevicomins have been determined. Prior discovery of common insect/elephant pheromones in Asian elephants, namely, (Z)-7-dodecenyl acetate and frontalin, suggests that the present findings may yield valuable insights into chemical communication among African elephants.

Topics: Animals; Aphids; Bridged Bicyclo Compounds, Heterocyclic; Coleoptera; Elephants; Female; Pheromones; Sesquiterpenes

Two major volatile constituents of the male mouse preputial gland, E,E-alpha-farnesene and E-beta-farnesene, were examined for their role in inducing estrous cycles in grouped female mice. The results indicated that the mixture of the farnesenes was as effective as the homogenate of the intact preputial gland, while the extract of the castrate preputial tissue did not show a pronounced response.

Topics: Animals; Chemoreceptor Cells; Estrus; Exocrine Glands; Female; Male; Mice; Mice, Inbred ICR; Sesquiterpenes; Time Factors

Five structurally diverse small ligands, all binding to the major urinary protein (MUP) of the male house mouse, show individually puberty-accelerating pheromonal activity in the recipient females. A recombinant MUP (identical structurally to the natural protein) has shown no biological activity. While four of these ligands were previously implicated in oestrus synchronization (Whitten effect), the same chemosignals now appear responsible for both sexual maturation and cycling in adult females.

Topics: Animals; Bridged Bicyclo Compounds, Heterocyclic; Female; Ketones; Ligands; Male; Mice; Mice, Inbred ICR; Molecular Structure; Pheromones; Proteins; Recombinant Fusion Proteins; Sesquiterpenes; Sexual Maturation; Thiazoles

Two sesquiterpenic compounds, E,E,-alpha-farnesene and E-beta-farnesene, which were previously found as major constituents of the male mouse preputial glands, were tested for their attractiveness to female mice. Sexually naive and sexually experienced females were given the opportunity to choose between natural stimuli and synthetic analogs of preputial chemosignals. Naive females preferred investigating the odors of intact males' urine and synthetic farnesenes when spiked in high concentration in bladder urine or water over control stimulus (water or bladder urine alone). Investigatory preference was not observed when synthetic farnesenes were presented to naive females in low concentration, i.e., only twice the natural content in the dominant male urine. However, sexually experienced females were clearly able to recognize and prefer samples with synthetic farnesenes, even in low concentration. We suggest that those sesquiterpenic compounds may play a wide-ranging role in the female recognition of sexually mature and socially dominant males.

Topics: Aggression; Animals; Exocrine Glands; Female; Genitalia, Male; Male; Mice; Mice, Inbred ICR; Sesquiterpenes; Sex Attractants; Sexual Behavior, Animal; Smell

Two terpenic constituents, E,E,-alpha-farnesene and E-beta-farnesene, were found to be elevated in dominant male urine when compared to subordinate or control males. These two urinary compounds were absent in the bladder urine of males; however, they were the most prominent constituents of the perputial gland's aliquots. The results of a two-choice preference test, conducted on ICR/Alb subordinate males, gave a strong indication that these two terpenic constituents introduced into the previously attractive stimulus significantly discouraged prolonged investigations by male mice. The compounds, whether present in the urine matrix or water, rendered the stimulus with a quality behaviorally similar to the urine of dominant males. It appears that they may be synonymous with the previously described aversion signal produced by dominant males. We suggest that these compounds may play a wide-ranging role in the territorial marking behavior of male mice.

Topics: Animals; Behavior, Animal; Chromatography; Dominance-Subordination; Female; Male; Mice; Mice, Inbred ICR; Molecular Structure; Pheromones; Sesquiterpenes; Social Dominance; Territoriality