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Requirements for Endothelin type-A receptors and Endothelin-1 signaling in the facial ectoderm for the patterning of skeletogenic neural crest cells in zebrafish gastritis cancer purchase reglan 10mg with visa. Reconstruction of the vertebrate ancestral genome reveals dynamic genome reorganization in early vertebrates gastritis symptoms lightheadedness purchase reglan. A medaka gene map: the trace of ancestral vertebrate proto-chromosomes revealed by comparative gene mapping gastritis tips quality 10 mg reglan. Expansion of signaling genes for adaptive immune system evolution in early vertebrates gastritis and celiac diet buy reglan with a mastercard. Mitteilungen des Hamburgischen Zoologischen Museums und Institut:Ergänzungsband zu Band 61, Kosswig-Festschrift. Pigment cell refugia in homeotherms-the unique evolutionary position of the iris. Chemical characterization of eumelanins with special emphasis on 5,6-dihydroxyindole-2-carboxylic acid content and molecular size. Timing and mechanism of ancient vertebrate genome duplications - the adventure of a hypothesis. Homology and the evolution of novelty during Danio adult pigment pattern development. Mutational analysis of endothelin receptor b1 (rose) during neural crest and pigment pattern development in the zebrafish Danio rerio. An orthologue of the kit related gene fms is required for development of neural crest-derived xanthophores and a subpopulation of adult melanocytes in the zebrafish, Danio rerio. Zebrafish sparse corresponds to an orthologue of c-kit and is required for the morphogenesis of a subpopulation of melanocytes, but is not essential for hematopoiesis or primordial germ cell development. Ednrb2 orients cell migration towards the dorsolateral neural crest pathway and promotes melanocyte differentiation. Involvement of endothelin receptors in normal and pathological development of neural crest cells. Subfunction partitioning, the teleost radiation and the annotation of the human genome. Genetic analysis of cavefish reveals molecular convergence in the evolution of albinism. Genetic effect on fine structure and development of pigment granules in mouse hair bulb melanocytes. The interaction of sexually and naturally selected traits in the adaptive radiations of cichlid fishes. Adaptive sequence evolution in a color gene involved in the formation of the characteristic egg-dummies of male haplochromine cichlid fishes. Insights from a sea lamprey into the evolution of neural crest gene regulatory network. Independent sorting-out of thousands of duplicated gene pairs in two yeast species descended from a whole-genome duplication. Tyrosinase and tyrosinase related protein 1 alleles specify domestic cat coat color phenotypes of the albino and brown loci. A mutation in the silver gene leads to defects in melanosome biogenesis and alterations in the visual system in the zebrafish mutant fading vision. Die geschlechtsbestimmende Region des Platyfisches Xiphophorus maculatus auf den Geschlechtschromosomen X und Y: Molekulare Analyse der genomischen Struktur und molekulargenetische Untersuchung von Genkandidaten. Molecular analysis of the sex-determining region of the platyfish Xiphophorus maculatus. Evolution of melanocortin receptors in teleost fish: the melanocortin type 1 receptor. Reciprocal gene loss between Tetraodon and zebrafish after whole genome duplication in their ancestor. Preferential subfunctionalization of slow-evolving genes after allopolyploidization in Xenopus laevis. Interrelationships of Atherinomorpha (medakas, flyingfishes, killifishes, silversides, and their relatives): the first evidence based on whole mitogenome sequences. Comparative genomics of ParaHox clusters of teleost fishes: gene cluster breakup and the retention of gene sets following whole genome duplications. A genome-wide survey of genes for enzymes involved in pigment synthesis in an ascidian, Ciona intestinalis. Embryonic development of the platyfish (Platypoecilus) and the swordtail (Xiphophorus), and their hybrids. Comparative genomics provides evidence for an ancient genome duplication event in fish. Major events in the genome evolution of vertebrates: paranome age and size differ considerably between ray finned fishes and land vertebrates. Human cell type diversity, evolution, development, and classification with special reference to cells derived from the neural crest. Origin and evolution of the neural crest: a hypothetical reconstruction of its evolutionary history. Genome duplications of early vertebrates as a possible chronicle of the evolutionary history of the neural crest. Evolution of gene networks by gene duplications: a mathematical model and its implications on genome organization. A model for divergent, allopatric speciation of polyploid pteridophytes resulting from silencing of duplicate-gene expression. The preferential retention of starch synthesis genes reveals the impact of whole-genome duplication on grass evolution. Molecular and functional evidence for early divergence of an endothelin-like system during metazoan evolution: analysis of the Cnidarian, hydra. The pteridine pathway in zebrafish: regulation and specification during the determination of neural crest cell-fate. The endothelin system: evolution of vertebrate-specific ligand-receptor interactions by three rounds of genome duplication Molecular Biology and Evolution, in press 7. The evolution of teleost pigmentation and the fish-specific genome duplication Journal of Fish Biology 73:1891-1918. Functional evolution of tyrp1 genes involved in melanin synthesis after duplication in fish manuscript 7. Linkage of sex determination and pigmentation genes might facilitate speciation (Streelman et al. A primary example for this phenomenon is the guppy (Poecilia reticulata), where many conspicuous color patterns are linked to the sex chromosomes (Lindholm and Breden 2002). Several highly polymorphic color patterns are also encoded by loci located on the sex chromosomes of another poeciliid, the southern platyfish Xiphophorus maculatus (Kallman 1975; Basolo 2006). All these pigmentation loci are present in the pseudoautosomal region and are not sex-specific, but some are more strongly expressed in males (Basolo 2006). Some of the pigmentation loci appear to be under sexual selection (Fernandez and Morris 2008). Although the genetic basis of color patterns has been investigated for almost one century in X. A2): Dorsal red (Dr) is located on the X chromosome and leads to orange red pigmentation of the dorsal fin. Anal red (Ar) is present on the Y chromosome and causes orange Dr Dr red coloration of the anal fin. Therefore, females of this platyfish strain (genotype X /X) have a red Dr Ar dorsal fin, but an inconspicuous, dull anal fin. Male individuals (genotype X /Y), in contrast, have a red dorsal fin as well as a red colored gonopodium, which is a specialized form of the anal fin in male poeciliids used as copulatory organ for internal fertilization. B) Close-up of the dorsal fin shows dark red xantho-erythrophores, yellow xanthophores and black melanophores surrounding two fin rays. C) Close-up of the gonopodium with red xantho-erythrophores and black melanophores. E) Close-up of the caudal fin shows yellow xanthophores and black melanophores surrounding two fin rays.
Additional findings include diffuse oedema chronic gastritis for years discount 10mg reglan with amex, petechial haemorrhages in the brain parenchyma surrounding ruptured vessels gastritis esophagitis buy cheap reglan on line, and ring haemorrhages gastritis diet òàíêè buy cheap reglan 10 mg online. Prospective studies from Malawian children with cerebral malaria show a prevalence of retinopathy around 60% in children with severe malaria (Beare gastritis mayo clinic purchase reglan once a day, Southern et al. The mortality rate in cerebral malaria remains high (>10%), despite the initiation of appropriate anti-malarial therapy. Prognostic biomarkers that could identify individuals at risk of poor outcomes would enable better allocation of resources and could select a high-risk group, in whom novel treatment modalities could be evaluated. We show that decreases in Ang-1, and increases in Ang-2 and sTie-2 are associated with retinopathy, clinical markers of disease severity, and mortality. Finally, we show that Ang-2 is a useful prognostic biomarker on its own or in combination with clinical findings at admission. This study represents a retrospective case control design of children with clinically defined cerebral malaria with retinopathy and mortality as outcome measures. Samples were selected based on the outcomes measures, the date of admission and sample availability, without any knowledge of clinical details. Retinopathy was defined by the presence of any one of the following retinal findings: haemorrhaging, whitening, or vessel changes with or without papilloedema, as previously described (Beare, Taylor et al. Clinical grading of retinal changes were recorded as follows: 0-4 for haemorrhages (0=none, 1= mild (1-5 haemorrhages), 2= moderate (5-20 haemorrhages), 3= severe (20-50 haemorrhages), 4= very severe (50+ haemorrhages)), and 0-3 for papilloedema, retinal whitening, orange vessels, white vessels, and white capillaries (0=none, 1=mild, 2=moderate, 3=severe) (Harding, Lewallen et al. The samples were then diluted in reagent diluent and standard curves were generated using recombinant proteins (R&D Systems). For Ang-1 and Ang-2, the detection antibodies were resuspended one hour prior to use with 2% heat inactivated goat or mouse serum respectively. Comparisons of proportions were based on Pearson chi square test, linear-by-linear association, or Fisher‟s exact test, as appropriate. Variables were excluded from multivariate models if >5% of the data was missing (to limit bias and a reduction 166 of power); the exception was thrombocytopenia, as platelets are a known source of Ang-1. All variables except age were dichotomized prior to inclusion in the logistic regression models to circumvent issues of non-linearity and multicollinearity. Linearity of age with the log odds of the dependent (retinopathy and mortality) was confirmed by including a Box-Tidwell transformation into the model and ensuring that this term was not significant. Models were validated by ensuring the Hosmer-Lemeshow goodness-of-fit test was not significant (p>0. There were 50 subjects that were retinopathy negative, 103 that were retinopathy positive, and 2 who died before fundoscopic exams could be performed. All subjects had plasma samples and clinical characteristics collected at admission. The demographic and clinical characteristics and laboratory findings at admission are summarized in Table 7. Demographic and clinical characteristics of population at admission Characteristic All Retinopathy Retinopathy P value Survivors Deaths P (n= 155) Negative (n= Positive (n= (n=96) (n= 59) value 50) 103) Demographic Age, median 34 43 32 0. The association of demographic, clinical and laboratory findings with retinopathy were evaluated: children with malaria retinopathy were significantly younger, and were more likely to have respiratory distress, severe anaemia and thrombocytopaenia compared to children without retinopathy (Table 7. Endothelial biomarkers and lactate are associated with retinopathy in children with cerebral malaria. Bar graphs showing the median and scatter of endothelial biomarkers and venous lactate. Analysis by Mann-Whitney (U statistic, p-value), *significant after Holms correction for 5 pair-wise comparisons: (A) Ang-1 (1969, p=0. Ang-2 and sTie-2 remained independent predictors of retinopathy after adjusting for covariates (age, respiratory distress, severe anaemia, thrombocytopaenia). Only one child had papilloedema without other retinal changes; whereas 33% (n=30) of retinopathy positive children had papilloedema, and 53. Venn-diagram depicting the distribution of retinal changes in the study population A Venn diagram depicting the distribution of retinal changes according to the number of children with haemorrhages (H), retinal whitening (W), or vessel abnormalities (V: orange vessels, white vessels, white capillaries). Detailed classification of retinal changes was available for 91 of the 103 retinopathy positive children. There was significant overlap between the various components of retinopathy with 51. Ang-2 and sTie-2 were positively associated with the number of haemorrhages, the severity of retinal whitening, and the number and extent of white vessels and capillaries (Table 7. Angiopietins and lactate correlate with the severity score of retinal abnormalities Biomarker Haemorrhage Whitening Orange White White Papilloedema Vessels vessels capillaries Ang-1 -0. Haemorrhage (0=none, 1= mild, 2=moderate, 3=severe, 4=very severe); Whitening, orange vessels, white vessels, white capillaries, and papilloedema (0=none, 1=mild, 2=moderate, 3=severe). Increased sTie-2 was associated with an increase in respiratory rate and white blood cell count (p<0. Correlation of the angiopoietin-Tie-2 system with clinical characteristics at admission Ang-1 Ang-2 sTie-2 Age (months) 0. Increases in median levels of Ang-2 and sTie-2, but not Ang-1, were associated with a fatal outcome (Figure 7. The relationship between endothelial biomarkers and mortality were further explored following dichotomization; and positive biomarker tests were associated with increased odds of death (Table 7. Ang-2 and Ang-1 remained independent predictors of mortality after adjusting for covariates (age, respiratory distress, Blantyre Coma Score, severe anaemia). Finally, using Kaplan-Meier curves, we examined the time to death for children stratified by biomarker test results. Kaplan-Meier estimates of survival based on Ang-2 levels at admission Children were stratified based on whether they had high Ang-2 levels (>3. A clinically predictive model of mortality was generated using parameters that were associated with poor outcome and are readily available to clinicians (age, Blantyre coma score, respiratory distress, severe anemia). Then, using the clinical model as a foundation, we added in the biomarker tests to determine whether they would significantly improve the predictive ability. In order to minimize cost and maximize practicality, we assessed whether a more parsimonious model could be achieved using a single biomarker. When all variables significantly associated with death are included in the analysis, the program generates a decision tree using Ang-2 at a cut-off of 3. To this aim, we examined how changes in levels of Ang-1, Ang-2 and sTie-2 related to retinopathy, clinical markers of disease severity and outcome. We demonstrate that perturbations in the angiopoietin-Tie-2 system are independently associated with retinopathy; and levels of Ang-2 and sTie-2 are related to the severity of haemorrhages, retinal whitening and vessels changes in the retina. The prognostic ability of the angiopoietins was also evaluated, and we found elevations in Ang-2 and sTie-2, and decreases in Ang-1 were associated with increased odds of death. Together, these data demonstrate an association between the angiopoietins and the microvascular disturbances involved in cerebral malaria pathogenesis. Angiopoietins engage the Tie family of receptor tyrosine kinases on the vascular endothelium to exert their effects. The most well characteristised members of this family are Tie-2 ligands Ang 1 and Ang-2. Ang-1 is released from mural cells (vascular smooth muscle cells and pericytes) and activated platelets and helps promote endothelial cell survival and helps maintain the integrity of endothelial tight junctions through the phosphorylation of Tie-2 (Milner, Hansen et al. A soluble form of Tie-2 has been identified in supernatants from cultured endothelial cells, as well as in normal human sera and plasma (Reusch, Barleon et al. Recent data suggest that Tie 2 shedding is dependent on matrix metalloproteinase-14 (Onimaru, Yonemitsu et al. To date, the function of sTie-2 is incompletely understood, as Tie-2 can bind several ligands with both activating (Ang-1, Ang-4) and inhibitory (Ang-2) functions; however, its association with cancer metastasis suggests a role for sTie-2 in regulating angiogenesis (Figueroa-Vega, Alfonso Perez et al. As the retina and the brain are formed from the same embryonic tissue and have analagous blood-tissue-barriers, investigations into the pathophysiology of retinopathy can provide critical insights into microvascular and tissue disturbances in the brain; as illustrated by the correlation between the number hemorrhages in the retina to those seen in brain (White, Lewallen et al. The accessibility of the retina enables clinicians and researchers to use indirect ophthalmoscopy to visualize subtle vascular and tissue changes in the eye, which cannot be appreciated in the brain using standard immunohistochemistry. In addition, fluorescein angiography has been used to visualize the extravasation of fluorescein corresponding to vascular leak (Beare, Harding et al. In this study, retinopathy was associated with a younger median age, respiratory distress, history of convulsions, severe anemia, thrombocytopenia and increased lactate (Figure 7.
Thiamin is water soluble and cooking water should be retained in the recipe made to treating gastritis over the counter buy 10 mg reglan visa prevent loss chronic gastritis frequently leads to order reglan 10mg line. Cooking the food to gastritis diet ïùùïäó purchase 10 mg reglan with mastercard just done stage and avoiding use of soda in preparation gastritis uptodate buy reglan 10 mg without prescription, helps to retain most of the thiamin in the preparation. Water-soluble Vitamins 103103103103103 Effect of Deficiency : When thiamin intake is deficient, the digestive system is disturbed resulting in loss of appetite (anorexia), poorly toned muscles and constipation. Some of the symptoms observed are mental depression, moodinesss, irritability, forgetfulness, confusion and fear. Severe deficiency leads to beri-beri, a disease of the nervous system, which has been known since antiquity. The name ‘beri beri’ is a Singhalese word meaning ‘I can’t I can’t’, which describes the disease, as the person is always too ill to do anything. Thiamin deficiency is found in association with chronic alcoholism, due to very low food intake and increased demand. It is a yellow-green (Latin word ‘flavus’ means yellow) fluorescent pigment containing the sugar ‘ribose’, hence the name riboflavin. It is less soluble in water than thiamin and more stable to heat, especially in acid solutions. For example, prolonged exposure of milk to direct sunlight may decrease the riboflavin content of milk considerably. Riboflavin functions as a vital part of coenzymes in both energy production and tissue protein building. It is thus essential for tissue health and growth of all animal and plant life (including microorganisms). It plays an important role in maintaining the integrity of mucocutaneous structures. So also are products derived from milk such as yoghurt (curds), butter milk, milk powder and concentrated milk (Table 9. There is no riboflavin in butter and ghee because the vitamin is water-soluble and remains in the water extract during the removal of butter from milk or curds. Recommended Daily Allowance the requirements of riboflavin have been determined by recording urinary excretion and the concentration of the vitamin in blood cells. The need for riboflavin increases during pregnancy and lactation and also with increased activity and caloric intake. The disease conditions, in which increased riboflavin in the diet is called for include, 104104104104104 Fundamentals of Foods, Nutrition and Diet Therapy recovery from wasting diseases, convalescence (for rebuilding of tissues), diarrhoea and vomitting (to make up for poor absorption). Water-soluble Vitamins 105105105105105 Effect of Deficiency: Lack of riboflavin affects the eyes, skin and nerves. The skin changes are found around the area of the mouth, on the lips, tongue and nose. The lips become inflamed, cracks are observed at the corners of the mouth and the tongue is swollen, red and sore. These are clinically known as cheilosis, angular stomatitis, naso-labial dyssebacia and scrotal dermititis. Niacin Goldberger in 1915 observed the existence of a pellagra-preventing factor, which he related to B vitamins. In 1937 Elvehjem and coworkers discovered that nicotinic acid was effective in curing black tongue in dogs. Cowgill suggested that the term ‘niacin’ be used for nicotinic acid to avoid association with the nicotine of tobacco. Niacin, the term which includes both nicotinic acid and nicotinamide, is another vitamin of the B-complex group. The amide is very soluble in water and is the one preferred therapeutically because it has no side reactions. The full name is nicotinamide adenine dinucleotide and its phosphate derivative respectively. These coenzymes are involved in tissue respiration and synthesis and the breakdown of glucose to produce energy. Niacin works in close association with riboflavin and thiamin in the cell metabolism system that produces energy. Requirements: All the factors, which affect energy needs, influence niacin requirement. Since one of the amino acids, tryptophan has been shown to be a precursor of niacin in the body, the total niacin requirement is stated in terms of ‘niacin equivalents’ to account for both sources. Niacin equivalents are calculated as follows: Tryptophan content in mg Niacin equivalents mg = Niacin content in mg + 60 Souces: In plant foods, groundnuts are the best source of niacin. Therefore cereals, which are used as staples, are the major source of niacin in the Indian diet, and they are supplemented by pulses and meat. Niacin equivalents are calculated as follows: b mgof tryptophan a+ = (mg of niacin) + = mg of niacin equivalents. Recommended Dietary Allowance Since niacin is involved in the utilisation of carbohydrates, the requirement of niacin is related to the total calories in the diet. The total niacin equivalent required daily on the basis of calorie requirement could range from 8 mg to 26 mg depending on the age and occupation of the individual (Table 9. Effect of Deficiency: Lack of niacin affects the skin, gastrointestinal tract and nervous system. Nervous changes include dizziness, insomnia, irritability, fear, depression and forgetfulness; later on there may be dementia. The deficiency disease is known as pellagra which is seen in endemic form in some parts of India, where jowar (sorghum) is the staple food. Pyridoxine Three naturally occurring pyridine derivatives (pyridoxine, pyridoxal and pyridoxamine) are known as vitamin B6. Functions: Vitamin B6 is a co-factor for several enzymes connected with the metabolism of amino acids. However, pulses, wheat and meat are known to be rich sources, while other cereals are fair sources. Requirements: There is some evidence that the pyridoxine requirements may be related to protein intake. Cooking losses in normal Indian diets are negligible; hence no allowances for losses need be made. Deficiency: the symptoms of vitamin B6 deficiency—such as peripheral neuritis, anaemia, glossitis, cheilosis and seborrhic dermatitis are similar to those of other B vitamins. Its name was derived from the Latin word folium, which means leaf, because it was first isolated from spinach leaves and is widely distributed in green, leafy plants. It is quite soluble in slightly alkaline or acid solution; but is reasonably stable in neutral or alkaline solutions, especially in the absence of air. Functions: the primary function of folic acid is related to the transfer of single carbon in the synthesis of a number of metabolites in the body. Folic acid undergoes a series of metabolic conversions to its various coenzyme forms after it is absorbed. It is a relatively stable vitamin but storage and cooking losses can be as high as 50 per cent, especially if cooking water is discarded. Suggested Daily Intake: the safe level of folate intake would be 100 mcg per day for adults and adolescents with 25 mcg in infancy increasing to 40 mcg at pre-school stage, gradually increasing with age to 100 mcg of folates at adolescence (Table 9. It was observed in one study that the birth weights of infants, born to mothers who had taken 300 mcg folate per day during pregnancy, were higher than those born to mothers who had received 100 or 200 mcg daily. The additional needs may be met through folate supplements, as it may be difficult to provide it in the diet. Deficiency: Prolonged and severe folic acid deficiency leads to abnormal formation of red blood cells resulting in megaloblastic anaemia. Water-soluble Vitamins 109109109109109 Vitamin B12 Vitamin B12 or cyanocobalamin was the last member of the B vitamins discovered in 1948. Cyanocobalamin is considered the most potent vitamin and is one of the last true vitamins that has been classified. It was discovered through studies of pernicious anaemia, a condition that begins with a megaloblastic anaemia and leads to an irreversible degeneration of the central nervous system. It was found that the condition could be reversed by feeding afflicted patients large amounts of raw liver. The active material in the liver was found to be vitamin B12, which is present only in very small amount. Cyanocobalamin contains a tetrapyrrole ring system, which is chemically very similar to the porphyrin ring system of the haeme compounds.
Syndromes
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A challenge to gastritis diet bland reglan 10mg cheap implementing these strategies lies in determining the underlying principles that govern megasynthase structure and assembly gastritis symptom of pregnancy cheap reglan master card. Development of these techniques will facili tate the discovery process and enhance production of therapeutics to gastritis symptoms dizziness buy reglan us fght tomorrow’s diseases gastritis gallbladder removal discount reglan 10mg line. Metabolic engineering is also being utilized by synthetic biologists to develop new drug delivery strategies. Synthetic biology [3], focuses on designing new biological systems from the assembly of bio logical parts. For example, many bacteria express proteins that confer the ability to adhere to and invade mammalian tissues. Future metabolic engineering eforts could combine the ability to selectively invade a diseased cell with the ability to produce a potent therapeutic. The end product would be an organism capable of seeking out, invading, and killing a diseased cell through the action of a locally-produced therapeutic. This example demonstrates how synthetic biology can expand the scope of metabolic engineering beyond industrial and specialty chemical production. Recently, sustainable energy production has become a major concern for scientists, government of cials, and the public. In the past four years (Jan 2004–Jan 2008), the price of oil has nearly tripled, reaching all-time highs that top $100 per barrel [33]. Simultaneously, concerns regarding fossil fuel supply and global climate change have strengthened the call for improved alternative energy sources. Metabolic engineering is already playing a role in address ing these concerns through the production of biofuels, chiefy ethanol. The production of ethanol from sugar cane in Brazil has become viable economically and now serves as a model for reducing depen dence on foreign oil [18]. However, research has shifed towards cellulosic feedstocks [12] such as corn stover, poplar, and switchgrass because corn-based ethanol has already had an impact on food prices (corn prices are up >150% per bushel between 2005 and 2008) [31]. Chapter 24 describes the progress made to date and the remaining challenges in bringing cellulosic ethanol to market. Ethanol, however, is not the only fuel microorganisms can be engineered to produce and is not nec essarily the ideal fuel for long-term sustainable energy generation. Biodiesel, a mix ture of acyl-esterifed fatty acids, is currently the second leading biofuel behind ethanol because of its compatibility with existing engines and its improved efciency relative to gasoline in internal com bustion engines. Biodiesel, which is typically made by transesterifying fats or oils with methanol, has been produced by a metabolically engineered strain of E. While current strains are not capable of producing biodiesel on an industrial scale, future metabolic engineering eforts may open the door to commercial production of cellulosic biodiesel. Other microbially-produced hydrocarbons including methane (methanogens), isoprene (Bacillus subtilis), C25-C31 olefns (microalgae), and C30-C37 terpenes (microalgae) have also attracted attention as biofuel candidates [7,26]. Metabolic engineers can develop production strategies for these hydrocarbons by either engineering native producers and/or heterologously expressing bio synthetic pathways in tractable hosts [24]. Sustainable production of liquid biofuels, whether alcohol or hydrocarbon, will require the use of cellulosic biomass as a feedstock. The challenge to this process is a complicated combination of discovering, expressing, and secreting enzymes capable of accessing the web of cellulose and hemicellulose fbers and efciently converting them into fermentable sugars. The conversion of sugars to fuels is a better understood process, but is still limited to those fuels whose biosynthese are currently known. Continued study of fuel producing organisms, through genome sequencing and biochemical characterization, will expand the list of potential fuels until the challenges of breaking down cellulosic biomass are solved. Metabolic engineers are also investigating pathways in phototosynthetic bacteria in order to bypass the complex issues surrounding biomass generation and breakdown. This approach to fuel production is environ mentally attractive because energy will be produced indirectly from sunlight, without the emission of greenhouse gases. Photoheterotrophic bacteria that can utilize hydrogen as a terminal point in electron transfer are the likely targets of metabolic engineering eforts to enhance production [16]. In addition to producing hydrogen, some phototrophic bacteria fx carbon dioxide to generate larger organic mol ecules that could be biosynthetically converted to biofuels. While ideal, engineering photosynthetic bacteria is not commonplace, and new metabolic engineering tools are required for these organisms. Alternatively, genes essential for photosynthesis and carbon fxation could be engineered into a more genetically tractable organism such as E. While promising, either choice will require signifcant research and engineering investments before commercial processes can be developed. In addition to the more apparent energy concerns, the rising price of oil is impacting the cost of other petrochemicals generated from fossil fuels. As a result, metabolic engineering is beginning to play a larger role in producing specialty chemicals for use in everyday products. This role will increase as oil prices continue to rise and the demand for sustainable production grows. Sustainable materials have been a focus of metabolic engineering eforts in which both natural biopolymers and traditional plastic monomers are produced from renewable resources. Despite these benefts, attempts to commercialize production in the 1980s–1990s (Biopol) failed because of high costs relative to petrochemical plastics [4]. Ongoing research is developing methods for sustainable biological production of plastic monomers and other specialty chemicals through biorefning. A biorefnery is analogous to a petroleum refnery where inputs are processed into a family of useful compounds, only biomass is used as an input to a biorefnery instead of petroleum [14]. In 2004, the Pacifc Northwest National Laboratory and the National Renewable Energy Laboratory distributed a list of the top value added chemicals derived from biomass [29]. The list was populated with natural metabolites (diacids, amino acids, reduced sugars) that could be readily con verted into other valuable commodities. In order for biorefneries to become reality, microorganisms need to be metabolically engineered to produce each of these central compounds in high yields from renewable feedstocks. This has been performed in a few cases and is best exemplifed by 1,3-propanediol, a component of commercial polyesters. DuPont has since teamed with Tate & Lyle to commercialize the process in order to generate bioplastics from renewable sugars [30]. Similar metabolic engineering strategies are underway to generate addi tional plastic monomers and further diversify the list of renewable chemical precursors. Chapter 22 expands beyond the ideas listed here by describing work to produce other classes of specialty chemicals through metabolic engineering of microorganisms. Viable production strategies for any of the mentioned targets will depend on new techniques to bal ance metabolite production and cell growth. Most organisms have evolved to survive in a dynamic environment, and when challenged with the overproduction of a particular compound, most organisms will evolve to alleviate associated stresses. If, however, production is seamlessly woven into the metabo lism of an organism and stresses are minimized, then a stable and efcient process can be developed. Chapter 21 describes the challenges in regulating a cell’s energy state, cofactor supply, and redox balance. Finally, as the felds of systems biology (from the top down) and synthetic biology (from the bottom up) clarify how metabolic parts interact, metabolic engineers will be able to construct increasingly sophisticated microorganisms to address the many sus tainability challenges facing our world. Process design for microbial plastic factories: metabolic engi neering of polyhydroxyalkanoates. Non-fermentative pathways for synthesis of branched-chain higher alcohols as biofuels. Production of the antima larial drug precursor artemisinic acid in engineered yeast. Nontemplate-dependent polymerization processes: polyhydroxyalkanoate synthases as a paradigm. Isoprene biosynthesis in Bacillus subtilis via the methyl erythritol phosphate pathway. It represents a strongly expanding feld, especially, as the number of available enzymes catalyzing industrially relevant reac tions and the knowledge about the metabolic pathways involved in biocatalytic processes is rapidly increasing. Enzymes catalyze a huge variety of reactions in order to synthesize the building blocks and to generate the energy necessary for growth and proliferation of living organisms. Two diferent synthesis strategies can be distinguished in biocatalysis: (i) Fermentations make use of the (modifed) metabolic network of microorganisms and the product of choice is derived from the growth substrate.
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