Isoprenoid Molecules Research Articles

Prenylation Defects and Oxidative Stress Trigger the Main Consequences of Neuroinflammation Linked to Mevalonate Pathway Deregulation.

The cholesterol biosynthesis represents a crucial metabolic pathway for cellular homeostasis. The end products of this pathway are sterols, such as cholesterol, which are essential components of cell membranes, precursors of steroid hormones, bile acids, and other molecules such as ubiquinone. Furthermore, some intermediates of this metabolic system perform biological activity in specific cellular compartments, such as isoprenoid molecules that can modulate different signal proteins through the prenylation process. The defects of prenylation represent one of the main causes that promote the activation of inflammation. In particular, this mechanism, in association with oxidative stress, induces a dysfunction of the mitochondrial activity. The purpose of this review is to describe the pleiotropic role of prenylation in neuroinflammation and to highlight the consequence of the defects of prenylation.

Optimization of the Isopentenol Utilization Pathway for Isoprenoid Synthesis in Escherichia coli.

Engineering microbes to produce isoprenoids can be limited by the competition between product formation and cell growth because biomass and isoprenoids are naturally derived from central metabolism. Recently, a two-step synthetic pathway was developed to partially decouple isoprenoid formation from central carbon metabolism. The pathway used exogenously added isopentenols as substrates. In the present study, we systematically optimized this isopentenol utilization pathway in Escherichia coli by comparing enzyme variants from different species, tuning enzyme expression levels, and using a two-stage process. Under the optimal conditions found in this study, ∼300 mg/L lycopene was synthesized from 2 g/L isopentenol in 24 h. The strain could be easily modified to synthesize two other isoprenoid molecules efficiently (248 mg/L β-carotene or 364 mg/L R-(-)-linalool produced from 2 g/L isopentenol). This study lays a solid foundation for producing agri-food isoprenoids at high titer/productivity from cost-effective feedstocks.

Identification of foods that affect the anti-cancer activity of pitavastatin in cells.

Statins inhibit the synthesis of mevalonate, a precursor isoprenoid molecule to geranylgeraniol that is necessary for the post-translational modification of several small GTPase oncogenes. Despite numerous preclinical studies suggesting that statins can be effective anticancer agents, prospective clinical trials have failed to demonstrate any clinical benefit in patients with cancer. We previously demonstrated that geranylgeraniol suppresses the activity of statins in cell culture studies, and that pitavastatin can cause regression of ovarian cancer xenografts in mice if the animals' diet is modified to avoid the inclusion of geranylgeraniol. Dietary sources of geranylgeraniol may consequently limit the activity of statins in cancer clinical trials. The present study tested several foods to identify those that affected the cytotoxic activity of pitavastatin towards ovarian cancer cells. Solvent extracts of several foods were tested for their ability to suppress the effects of pitavastatin in cell growth assays. The results revealed that pitavastatin induced cell death in ovarian cancer cells (IC50=5.2 µM) and this was blocked by geranylgeraniol whereas other products of the mevalonate pathway (coenzyme Q, dolichol or cholesterol) had no effect on the activity of pitavastatin in cell growth assays. Solvent extracts from several foods, especially oils (apart from rapeseed), also blocked the cytotoxic activity of pitavastatin. Several extracts from a range of fruit, vegetables and carbohydrate-rich foods also did not block the activity of pitavastatin. However, extracts from beans, lettuce, oats, eggs and various nuts reduced the activity of pitavastatin. These data identified foods that patients could eat to potentially improve the outcome of clinical trials of pitavastatin in cancer.

Bioprospecting potentials of moderately halophilic bacteria and the isolation of squalene producers from Kuwait sabkha.

Sabkhas in Kuwait are unique hypersaline marine environments under-explored for bacterial community composition and bioprospecting. The 16S rRNA sequence analysis of 46 isolates with distinct morphology from two Kuwait sabkhas recovered 11 genera. Phylum Firmicutes dominated these isolates, and Bacillus (32.6%) was recovered as the dominant genera, followed by Halococcus (17.4%). These isolates were moderately halophilic, and some of them showed tolerance and growth at extreme levels of salt (20%), pH (5 and/or 11), and temperature (55 °C). A higher percentage of isolates harbored protease (63.0), followed by DNase (41.3), amylase (41.3), and lipase (32.6). Selected isolates showed antimicrobial activity against E. faecalis and isolated Halomonas shengliensis, and Idiomarina piscisalsi harbored gene coding fordNDP-glucose 4,6-dehydratase (Glu 1), indicating their potential to produce biomolecules with deoxysugar moieties. Palmitic acid or oleic acid was the dominant fatty acid, and seven isolates had some polyunsaturated fatty acids (linolenic or γ-linolenic acid). Interestingly, six isolates belonging to Planococcus and Oceanobacillus genus produced squalene, a bioactive isoprenoid molecule. Their content increased 30-50% in the presence of Terbinafine. The potential bioactivities and extreme growth conditions make this untapped bacterial diversity a promising candidate for future bioprospecting studies.

Synthesis of Naphthoquinone Derivatives: Menaquinones, Lipoquinones and Other Vitamin K Derivatives.

Menaquinones are a class of isoprenoid molecules that have important roles in human biology and bacterial electron transport, and multiple methods have been developed for their synthesis. These compounds consist of a methylnaphthoquinone (MK) unit and an isoprene side chain, such as found in vitamin K1 (phylloquinone), K2, and other lipoquinones. The most common naturally occurring menaquinones contain multiple isoprene units and are very hydrophobic, rendering it difficult to evaluate the biological activity of these compounds in aqueous assays. One way to overcome this challenge has been the application of truncated MK-derivatives for their moderate solubility in water. The synthesis of such derivatives has been dominated by Friedel-Crafts alkylation with BF3∙OEt2. This attractive method occurs over two steps from commercially available starting materials, but it generally produces low yields and a mixture of isomers. In this review, we summarize reported syntheses of both truncated and naturally occurring MK-derivatives that encompass five different synthetic strategies: Nucleophilic ring methods, metal-mediated reactions, electrophilic ring methods, pericyclic reactions, and homologation and side chain extensions. The advantages and disadvantages of each method are discussed, identifying methods with a focus on high yields, regioselectivity, and stereochemistry leading to a detailed overview of the reported chemistry available for preparation of these compounds.

Metabolic flux ratio analysis by parallel 13C labeling of isoprenoid biosynthesis in Rhodobacter sphaeroides

Metabolic engineering for increased isoprenoid production often benefits from the simultaneous expression of the two naturally available isoprenoid metabolic routes, namely the 2-methyl-D-erythritol 4-phosphate (MEP) pathway and the mevalonate (MVA) pathway. Quantification of the contribution of these pathways to the overall isoprenoid production can help to obtain a better understanding of the metabolism within a microbial cell factory. Such type of investigation can benefit from 13C metabolic flux ratio studies. Here, we designed a method based on parallel labeling experiments (PLEs), using [1-13C]- and [4-13C]glucose as tracers to quantify the metabolic flux ratios in the glycolytic and isoprenoid pathways. By just analyzing a reporter isoprenoid molecule and employing only four equations, we could describe the metabolism involved from substrate catabolism to product formation. These equations infer 13C atom incorporation into the universal isoprenoid building blocks, isopentenyl-pyrophosphate (IPP) and dimethylallyl-pyrophosphate (DMAPP). Therefore, this renders the method applicable to the study of any of isoprenoid of interest. As proof of principle, we applied it to study amorpha-4,11-diene biosynthesis in the bacterium Rhodobacter sphaeroides. We confirmed that in this species the Entner-Doudoroff pathway is the major pathway for glucose catabolism, while the Embden-Meyerhof-Parnas pathway contributes to a lesser extent. Additionally, we demonstrated that co-expression of the MEP and MVA pathways caused a mutual enhancement of their metabolic flux capacity. Surprisingly, we also observed that the isoprenoid flux ratio remains constant under exponential growth conditions, independently from the expression level of the MVA pathway. Apart from proposing and applying a tool for studying isoprenoid biosynthesis within a microbial cell factory, our work reveals important insights from the co-expression of MEP and MVA pathways, including the existence of a yet unclear interaction between them.

Induction of non-lamellar phases in archaeal lipids at high temperature and high hydrostatic pressure by apolar polyisoprenoids

It is now well established that cell membranes are much more than a barrier that separate the cytoplasm from the outside world. Regarding membrane's lipids and their self-assembling, the system is highly complex, for example, the cell membrane needs to adopt different curvatures to be functional. This is possible thanks to the presence of non-lamellar-forming lipids, which tend to curve the membrane. Here, we present the effect of squalane, an apolar isoprenoid molecule, on an archaea-like lipid membrane. The presence of this molecule provokes negative membrane curvature and forces lipids to self-assemble under inverted cubic and inverted hexagonal phases. Such non-lamellar phases are highly stable under a broad range of external extreme conditions, e.g. temperatures and high hydrostatic pressures, confirming that such apolar lipids could be included in the architecture of membranes arising from cells living under extreme environments.

A Metabolic Dependency for Host Isoprenoids in the Obligate Intracellular Pathogen Rickettsia parkeri Underlies a Sensitivity to the Statin Class of Host-Targeted Therapeutics.

Gram-negative bacteria in the order Rickettsiales have an obligate intracellular growth requirement, and some species cause human diseases such as typhus and spotted fever. The bacteria have evolved a dependence on essential nutrients and metabolites from the host cell as a consequence of extensive genome reduction. However, it remains largely unknown which nutrients they acquire and whether their metabolic dependency can be exploited therapeutically. Here, we describe a genetic rewiring of bacterial isoprenoid biosynthetic pathways in the Rickettsiales that has resulted from reductive genome evolution. Furthermore, we investigated whether the spotted fever group Rickettsia species Rickettsia parkeri scavenges isoprenoid precursors directly from the host. Using targeted mass spectrometry, we found that infection caused decreases in host isoprenoid products and concomitant increases in bacterial isoprenoid metabolites. Additionally, we report that treatment of infected cells with statins, which inhibit host isoprenoid synthesis, prohibited bacterial growth. We show that growth inhibition correlates with changes in bacterial size and shape that mimic those caused by antibiotics that inhibit peptidoglycan biosynthesis, suggesting that statins lead to an inhibition of cell wall synthesis. Altogether, our results describe a potential Achilles' heel of obligate intracellular pathogens that can potentially be exploited with host-targeted therapeutics that interfere with metabolic pathways required for bacterial growth.IMPORTANCE Obligate intracellular pathogens, which include viruses as well as certain bacteria and eukaryotes, are a subset of infectious microbes that are metabolically dependent on and unable to grow outside an infected host cell because they have lost or lack essential biosynthetic pathways. In this study, we describe a metabolic dependency of the bacterial pathogen Rickettsia parkeri on host isoprenoid molecules that are used in the biosynthesis of downstream products, including cholesterol, steroid hormones, and heme. Bacteria make products from isoprenoids, such as an essential lipid carrier for making the bacterial cell wall. We show that bacterial metabolic dependency can represent a potential Achilles' heel and that inhibiting host isoprenoid biosynthesis with the FDA-approved statin class of drugs inhibits bacterial growth by interfering with the integrity of the cell wall. This work supports the potential to treat infections by obligate intracellular pathogens through inhibition of host biosynthetic pathways that are susceptible to parasitism.

Vitamins (A&D) and Isoprenoid (Chenodeoxycholic acid) molecules are accompanied by Th1 immunostimulatory response and therapeutic cure in vivo: possible antileishmanial drugs

Investigation of immune modulatory anti-leishmanial molecules is now being strongly encouraged to overcome the immunosuppression manifested during visceral leishmaniasis (VL), resistance, toxicity and high cost associated with conventional therapeutics. In the present study, we explored the protective efficacy of vitamin D3, retinoic acid and isoprenoid chenodeoxycholic acid (CDCA) combinations against L. donovani infected BALB/c mice. We also probed the immune modulatory response (Th1 & Th2 cytokines) and infection dynamics following experimental infections with drug treated animals. Our results indicate that Vit.D3/RA and CDCA/RA combination treatment led to significant inhibition of parasite load on days 21 and 28 post treatment. Furthermore, there was a marked inhibition of Th2 type immune responses in IL-4, IL-5 and polarization of Th1 biased immunity along with upregulation of IL-1, IFN-γ, and TNF-α levels on day 28 post treatment. In addition, mice treated with Vit.D3/RA and CDCA/RA demonstrates here that splenic histological recovery against the virulent challenge of L. donovani by day 28 was comparable to control group. The conclusions derived from this study suggests that a combination of vitamin A, D3 and isoprenoids may have a potential immunomodulatory therapeutic role against leishmaniasis.

Comparative energetics of carbon storage molecules in green algae

Several members of the green algae possess the ability to produce lipids and/or high value compounds in significant quantities. While for several of these green algal species induction of increased lipid production has been shown, and cultivation of species for high value molecules occurs at production scale, the molecular mechanisms governing over-accumulation of molecules synthesized from isoprenoid precursors, carotenoids, for example, have received far less attention. Here, we present a calculation of the required ATP equivalencies per carbon atom and reducing power equivalencies as NADH/NADPH (NAD(P)H) per carbon atom for the isoprenoid molecules β-carotene (C40), astaxanthin (C40), and squalene (C30). We compared energetic requirements of carbohydrates, triacylglycerol, and isoprenoid molecules under a gradient of conditions of cellular stress. Our calculations revealed slightly less ATP and NAD(P)H equivalency per carbon atom between triacylglycerol and the three isoprenoid molecules. Based on our results, we propose that the driving force for differences in accumulation patterns of carotenoids vs. triacylglycerols in algal cells under stress is largely dependent on the presence and regulation of bypass mechanisms at metabolic junction bottlenecks, like pyruvate dehydrogenase (PDH), within particular species. We provide a discussion of several molecular mechanisms that may influence carbon partitioning within different groups of green algae, including metabolic inhibition through accumulation of specific substrates related to ATP and reducing equivalent production (NAD(P)H) as well as cellular compartmentalization. This work contributes to the ongoing discussion of cellular homeostatic regulation during stress, as well as the potential mechanisms driving long-term carbon storage as it relates to energy and redox states within the algal cell.

Abstract 4020: Identification and characterization of Novel MYC and p53 target molecules from medicinal plants of North East India

Abstract Background: Identification and characterization of novel molecular inhibitors that target key regulators of cancer stem cell (CSCs) self-renewal is promising in cancer therapeutics. MYC and p53, the two major cellular transcription factors, acts as key molecular regulators in stem cells and cancer stem cells self-renewal. While MYC enhances, p53 inhibits the self-renewal of stem cells. Thus, developing novel molecules that could potentially target either MYC and or p53 might potential therapeutic application. However, the search for small molecules that could target the self-renewal aspect of these two proteins has been elusive. Previously; we demonstrated that isoprenoid molecule squalene could enhance bone marrow hematopoietic and mesenchymal stem cells (MSCs) by modulating MYC. Importantly, we found that ursolic acid, an isoprenoid molecule found in Tulsi plant, inhibited HIF-1alpha, a transcription factor regulated by MYC and p53. Hence, having these prior experiences on isoprenoids, we speculate that novel isoprenoid may exist that could modulate MYC’s role in cancer self-renewal. We are especially interested in identifying novel isoprenoid molecules (metabolites of mevalonate pathway) found in medicinal plants of North East India, where KaviKrishna laboratory is located. Methods: For the study, we proposed to develop an in vitro self-renewal based assay platform(henceforth known as STEM-TECH platform) to identify novel molecules that act on self-renewal aspect of MYC and p53. In this assay, we subjected the oral cancer cell line SCC-25 to 3-D tumoringeic growth using methylcellulose based method. Using this assay, we have screened 20 herbal extracts of North East India, and selected 3 herbal extracts for further evaluation. For the in vivo study, we added these herbal extracts to drinking water of C57BL/6 mice treated with 4NQO (an oral carcinogen) and FVB/N mice with MYC-induced thymic lymphoma. The mice were observed for 10 weeks and subjected to evaluation of tumor growth, and also evaluation of cancer stem cells using ABCG2, a cell surface marker expressed by cancer stem cells. Results: We found that herbal extracts from Tulsi and Soalu exhibited strong anti-tumor activity in the in vivo mouse models. Importantly, these extracts exhibited the ability to inhibit the self-renewal of MYC driven ABCG2+ cancer cells (1). Also, these extracts were then subjected to in vitro Stem-Tech assay and we found that one herbal extract could modulate the transcriptional binding of MYC. Importantly, we found that squalene, an isoprenoid found in several herbal extracts in NE India could modulate MYC activity by an unknown mechanism. Conclusion: Our results indicate that the vast, untapped herbal plants available in India’s remote North East contain valuable herbal medicinal plant having potential MYC inhibitor. 1. Das B et al. MYC through HIF-2alpha regulates the self-renewal program in cancer stem cells (under review). Note: This abstract was not presented at the meeting. Citation Format: Sora Sandhya, Joyeeta Talukdar, Bidisha Pal, Seema Bhuyan, Debabrat Baishya, Bikul Das. Identification and characterization of Novel MYC and p53 target molecules from medicinal plants of North East India [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4020. doi:10.1158/1538-7445.AM2017-4020

Kinetic and Binding Studies of Streptococcus pneumoniae Type 2 Isopentenyl Diphosphate:Dimethylallyl Diphosphate Isomerase.

Type 2 isopentenyl diphosphate:dimethylallyl diphosphate isomerase (IDI-2) converts isopentenyl diphosphate (IPP) to dimethylallyl diphosphate (DMAPP), the two fundamental building blocks of isoprenoid molecules. IDI-2 is found in many species of bacteria and is a potential antibacterial target since this isoform is non-homologous to the type 1 enzyme in Homo sapiens. IDI-2 requires a reduced flavin mononucleotide to form the catalytically active ternary complex, IDI-2·FMNH2·IPP. For IDI-2 from the pathogenic bacterium Streptococcus pneumoniae, the flavin can be treated kinetically as a dissociable cosubstrate in incubations with IPP and excess NADH. Under these conditions, the enzyme follows a modified sequential ordered mechanism where FMN adds before IPP. Interestingly, the enzyme shows sigmoidal behavior when incubated with IPP and NADH with varied concentrations of FMN in aerobic conditions. In contrast, sigmoidal behavior is not seen in incubations under anaerobic conditions where FMN is reduced to FMNH2 before the reaction is initiated by addition of IPP. Stopped-flow experiments revealed that FMN, whether bound to IDI-2 or without enzyme in solution, is slowly reduced in a pseudo-first-order reaction upon addition of excess NADH (k(red)(FMN) = 5.7 × 10(-3) s(-1) and k(red)(IDI-2·FMN) = 2.8 × 10(-3) s(-1)), while reduction of the flavin is rapid upon addition of NADH to a mixture of IDI-2·FMN, and IPP (k(red)(IDI-2·FMN·IPP) = 8.9 s(-1)). Similar experiments with dithionite as the reductant gave k(red)(FMN) = 221 s(-1) and k(red)(IDI-2·FMN) = 411 s(-1). Dithionite reduction of FMN in the IDI-2·FMN and IPP mixture was biphasic with k(red)(IDI-2·FMN·IPP (fast)) = 326 s(-1) and k(red)(IDI-2·FMN·IPP (slow)) = 6.9 s(-1) The pseudo-first-order rate constant for the slow component was similar to those for NADH reduction of the flavin in the IDI-2·FMN and IPP mixture and may reflect a rate-limiting conformational change in the enzyme.

Mathematical modelling of the diurnal regulation of the MEP pathway in Arabidopsis.

Isoprenoid molecules are essential elements of plant metabolism. Many important plant isoprenoids, such as chlorophylls, carotenoids, tocopherols, prenylated quinones and hormones are synthesised in chloroplasts via the 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway. Here we develop a mathematical model of diurnal regulation of the MEP pathway in Arabidopsis thaliana. We used both experimental and theoretical approaches to integrate mechanisms potentially involved in the diurnal control of the pathway. Our data show that flux through the MEP pathway is accelerated in light due to the photosynthesis-dependent supply of metabolic substrates of the pathway and the transcriptional regulation of key biosynthetic genes by the circadian clock. We also demonstrate that feedback regulation of both the activity and the abundance of the first enzyme of the MEP pathway (1-deoxy-D-xylulose 5-phosphate synthase, DXS) by pathway products stabilizes the flux against changes in substrate supply and adjusts the flux according to product demand under normal growth conditions. These data illustrate the central relevance of photosynthesis, the circadian clock and feedback control of DXS for the diurnal regulation of the MEP pathway.

Bioprocess engineering for microbial synthesis and conversion of isoprenoids.

Isoprenoids represent a natural product class essential to living organisms. Moreover, industrially relevant isoprenoid molecules cover a wide range of products such as pharmaceuticals, flavors and fragrances, or even biofuels. Their often complex structure makes chemical synthesis a difficult and expensive task and extraction from natural sources is typically low yielding. This has led to intense research for biotechnological production of isoprenoids by microbial de novo synthesis or biotransformation. Here, metabolic engineering, including synthetic biology approaches, is the key technology to develop efficient production strains in the first place. Bioprocess engineering, particularly in situ product removal (ISPR), is the second essential technology for the development of industrial-scale bioprocesses. A number of elaborate bioreactor and ISPR designs have been published to target the problems of isoprenoid synthesis and conversion, such as toxicity and product inhibition. However, despite the many exciting applications of isoprenoids, research on isoprenoid-specific bioprocesses has mostly been, and still is, limited to small-scale proof-of-concept approaches. This review presents and categorizes different ISPR solutions for biotechnological isoprenoid production and also addresses the main challenges en route towards industrial application.

Distinct pathways of cholesterol biosynthesis impact on insulin secretion.

Results from previous investigations have indicated that glucose-stimulated insulin secretion (GSIS) is affected by changes in cholesterol and its intermediates, but the precise link between secretion and cholesterol has not been thoroughly investigated. In this study, we show the contribution of both protein isoprenylation and cholesterol-dependent plasma membrane structural integrity to insulin secretion in INS-1E cells and mouse islets. Acute (2 h) inhibition of hydroxyl-methylglutaryl-CoA reductase by simvastatin (SIM) resulted in inhibition of GSIS without reduction in total cellular cholesterol content. This effect was prevented by cell loading with the isoprenyl molecule geranylgeranyl pyrophosphate. Chronic (24 h) inhibition of cholesterol biosynthesis resulted in inhibition of GSIS with a significant reduction in total cellular cholesterol content, which was also observed after the inhibition of cholesterol biosynthesis downstream of isoprenoid formation. Electron paramagnetic resonance analyses of INS-1E cells showed that the SIM-induced reduction in cholesterol increased plasma membrane fluidity. Thus, the blockade of cholesterol biosynthesis resulted in the reduction of availability of isoprenoids, followed by a reduction in the total cholesterol content associated with an increase in plasma membrane fluidity. Herein, we show the different contributions of cholesterol biosynthesis to GSIS, and propose that isoprenoid molecules and cholesterol-dependent signaling are dual regulators of proper β-cell function.

Carotenoids in unexpected places: Gall midges, lateral gene transfer, and carotenoid biosynthesis in animals

Carotenoids are conjugated isoprenoid molecules with many important physiological functions in organisms, including roles in photosynthesis, oxidative stress reduction, vision, diapause, photoperiodism, and immunity. Until recently, it was believed that only plants, microorganisms, and fungi were capable of synthesizing carotenoids and that animals acquired them from their diet, but recent studies have demonstrated that two arthropods (pea aphid and spider mite) possess a pair of genes homologous to those required for the first step of carotenoid biosynthesis. Absent in all other known animal genomes, these genes appear to have been acquired by aphids and spider mites in one or several lateral gene transfer events from a fungal donor. We report the third case of fungal carotenoid biosynthesis gene homologs in an arthropod: flies from the family Cecidomyiidae, commonly known as gall midges. Using phylogenetic analyses we show that it is unlikely that lycopene cyclase/phytoene synthase and phytoene desaturase homologs were transferred singly to an ancient arthropod ancestor; instead we propose that genes were transferred independently from related fungal donors after divergence of the major arthropod lineages. We also examine variation in intron placement and copy number of the carotenoid genes that may underlie function in the midges. This trans-kingdom transfer of carotenoid genes may represent a key innovation, underlying the evolution of phytophagy and plant-galling in gall midges and facilitating their extensive diversification across plant lineages.

The role of carotenoids and their derivatives in mediating interactions between insects and their environment

Carotenoids are long conjugated isoprenoid molecules derived mainly from plants and microbial organisms. They are highly diverse, with over 700 identified structures, and are widespread in nature. In addition to their fundamental roles as light-harvesting molecules in photosynthesis, carotenoids serve a variety of functions including visual and colouring pigments, antioxidants and hormone precursors. Although the functions of carotenoids are relatively well studied in plants and vertebrates, studies are severely lacking in insect systems. There is a particular dearth of knowledge on how carotenoids move among trophic levels, influence insect multitrophic interactions and affect evolutionary outcomes. This review explores the known and potential roles that carotenoids and their derivatives have in mediating the ecological interaction of insects with their environment. Throughout the review, we highlight how the fundamental roles of carotenoids in insect physiology might be linked to ecological and evolutionary processes.

Functional properties of carotenoids originating from algae.

Carotenoids are isoprenoid molecules which are synthesised de novo by photosynthetic plants, fungi and algae and are responsible for the orange, yellow and some red colours of various fruits and vegetables. Carotenoids are lipophilic compounds, some of which act as provitamins A. These compounds can be divided into xanthophylls and carotenes. Many macroalgae and microalgae are rich in carotenoids, where these compounds aid in the absorption of sunlight. Industrially, these carotenoids are used as food pigments (in dairy products, beverages, etc.), as feed additives, in cosmetics and in pharmaceuticals, especially nowadays when there is an increasing demand by consumers for natural products. Production of carotenoids from algae has many advantages compared to other sources; for example, their production is cheap, easy and environmentally friendly; their extraction is easier, with higher yields, and there is no lack of raw materials or limited seasonal variation. Recently, there has been considerable interest in dietary carotenoids with respect to their antioxidant properties and their ability to reduce the incidence of some chronic diseases where free radicals are involved. Possibly, carotenoids protect cells from oxidative stress by quenching singlet oxygen damage with various mechanisms. Therefore, carotenoids derived from algae could be a leading natural resource in the research for potential functional ingredients.

Isoprenoid biosynthesis in bacterial pathogens

Isoprenoid biosynthesis is essential for cell survival. Over 35 000 isoprenoid molecules have been identified to date in the three domains of life (bacteria, archaea and eukaryotes), and these molecules are involved in a wide variety of vital biological functions. Isoprenoids may be synthesized via one of two independent nonhomologous pathways, the classical mevalonate pathway or the alternative 2C-methyl-D-erythritol 4-phosphate (MEP) pathway. Given that isoprenoids are indispensable, enzymes involved in their production have been investigated as potential drug targets. It has also been observed that the MEP pathway intermediate 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate (HMB-PP) can activate human Vγ9/Vδ2 T cells. Herein we review isoprenoid biosynthesis in bacterial pathogens. The role of isoprenoid biosynthesis pathways in host-pathogen interactions (virulence potential and immune stimulation) is examined. Finally, the design of antimicrobial drugs that target isoprenoid biosynthesis pathways is discussed.

Extensive Biodegradation of Nigerian Crude Oil (Escravos Light) by Newly Characterized Yeast Strains

Because microbial degradation is known to be an efficient process in the in situ decontamination of oil-bearing environments, it is believed that development of effective bioremediation strategies will be aided by microbial sourcing of novel and competent hydrocarbon degraders with a broad and unusual substrate spectrum. Thus, in keeping with this objective, two Candida strains (MN1 and MC1) isolated after a repeated batch enrichment technique were tested for their biodegradation potentials on Nigerian crude oil, Escravos light. Axenic cultures of strains MN1 and MC1 grew at a rate of 1.623 and 0.586 d−1, respectively, in mineral salts medium supplemented with 8.4 g L−1 of crude oil. Whereas strain MN1 degraded aliphatic fractions by 97.6% and the aromatics by 74.61%, the corresponding values obtained for MC1 were 97.2% and 67.29% during the 14-day incubation period. The gas chromatography (GC) fingerprinting of aliphatic fractions showed major degradation of heptadecane (C17), octadecane (C18), nonadecane (C19), eicosane (C20), undodecane (C21), tricosane (C23), hexacosane (C26), octacosane (C28), and nonacosane (C29) in less than 6 days, whereas nearly 100% of these fractions including the isoprenoid molecules was metabolized in 14 days. Among the aromatic fractions that were nearly eliminated during the cultivation period were naphthalene, phenanthrene, fluoranthrene, chrysene, benzo(a)anthracene, benzo(b)fluoranthrene, and benzo(a)pyrene. Interestingly, substrate uptake studies showed that both strains grew very well on petroleum cuts, biphenyl, phenol, xylene, and quite a number of polycyclic aromatic hydrocarbons including pyrene, phenanthrene, and anthracene.