Multi-catalysis reactions: new prospects and challenges of biotechnology to valorize lignin

Considerable effort has been dedicated to the chemical depolymerization of lignin, a biopolymer constituting a possible renewable source for aromatic value-added chemicals. However, these efforts yielded limited success up until now. Efficient lignin conversion might necessitate novel catalysts enabling new types of reactions. The use of multiple catalysts, including a combination of biocatalysts, might be necessary. New perspectives for the combination of bio- and inorganic catalysts in one-pot reactions are emerging, thanks to green chemistry-driven advances in enzyme engineering and immobilization and new chemical catalyst design. Such combinations could offer several advantages, especially by reducing time and yield losses associated with the isolation and purification of the reaction products, but also represent a big challenge since the optimal reaction conditions of bio- and chemical catalysis reactions are often different. This mini-review gives an overview of bio- and inorganic catalysts having the potential to be used in combination for lignin depolymerization. We also discuss key aspects to consider when combining these catalysts in one-pot reactions.     

Lignins and lignocellulosics: a better control of synthesis for new and improved uses

The composition and structure of lignified walls has a dramatic impact on the technological value of raw materials. The chemical flexibility of the secondary cell wall has been demonstrated and it is now possible to develop strategies to optimize its composition through genetic engineering. Thanks to functional genomics, new target genes of both plant and microbial origin are rapidly becoming available for this purpose and their use will open new avenues for producing tailor-made plant products with improved properties. Moreover, the major proportion of terrestrial plant biomass comprises lignified cell walls and this reservoir of carbon should be increasingly exploited for the production of chemicals and energy within the context of sustainable development. For example, the design of plants suitable for downstream conversion processes, such as the production of bioethanol, and the exploitation of microorganisms and microbial enzymes for biomass pretreatments or for the production of novel chemicals.     

Routes to Potential Bioproducts from Lignocellulosic Biomass Lignin and Hemicelluloses

An essential feature of proposed fermentation-based lignocellulose to biofuel conversion processes will be the co-production of higher value chemicals from lignin and hemicellulose components. Over the years, many routes for chemical conversion of lignin and hemicelluloses have been developed by the pulp and paper industry and we propose that some of these can be applied for bioproducts manufacturing. For lignin products, thermochemical, chemical pulping, and bleaching methods for production of polymeric and monomeric chemicals are reviewed. We conclude that peroxyacid chemistry for phenol and ring-opened products looks most interesting. For hemicellulose products, preextraction of hemicelluloses from woody biomass is important and influences the mixture of solubilized material obtained. Furfural, xylitol, acetic acid, and lactic acid are possible targets for commercialization, and the latter can be further converted to acrylic acid. Pre-extraction of hemicelluloses can be integrated into most biomass-to-biofuel conversion processes.     

Botanochemicals: Supplements to petrochemicals

The development of alternative sources for energy and chemicals, particularly the use of plant biomass as a renewable resource for fuel or chemical feedstocks has received much recent attention. This report reviews the chemical utilization of plant materials for liquid fuels or organic chemicals, and presents the possibility of producing hydrocarbon and related chemical products, directly or indirectly, from extant plants rather than from fossil sources such as petroleum or coal.     

Direct production of commodity chemicals from lignocellulose using Myceliophthora thermophila

The production of fuels and chemicals from renewable plant biomass has been proposed as a feasible strategy for global sustainable development. However, the economic efficiency of biorefineries is low. Here, through metabolic engineering, Myceliophthora thermophila, a cellulolytic thermophilic fungus, was constructed into a platform that can efficiently convert lignocellulose into important bulk chemicals—four carbon 1, 4-diacids (malic and succinic acid), building blocks for biopolymers—without the need for extra hydrolytic enzymes. Titers of >200 g/L from crystalline cellulose and 110 g/L from plant biomass (corncob) were achieved during fed-batch fermentation. Our study represents a milestone in consolidated bioprocessing technology and offers a new and promising system for the cost-effective production of chemicals and fuels from biomass.     

Prediction of toxicity from chemical structure

The basis for the prediction of toxicity from chemical structure is that the properties of a chemical are implicit in its molecular structure. Biological activity can be expressed as a function of partition and reactivity, that is, for a chemical to be able to express its toxicity, it must be transported from its site of administration to its site of action and then it must bind to or react with its receptor or target. This process may also involve metabolic transformation of the chemical. The application of these principles to the prediction of the toxicity of new or untested chemicals has been achieved in a number of different ways covering a wide range of complexity, from computer systems containing databases of hundreds of chemicals, to simple "reading across" between chemicals with similar chemical/toxicological functionality. The common feature of the approaches described in this article is that their starting point is a mechanistic hypothesis linking chemical structure and/or functionality with the toxicological endpoint of interest. The prediction of toxicity from chemical structure can make a valuable contribution to the reduction of animal usage in the screening out of potentially toxic chemicals at an early stage and in providing data for making positive classifications of toxicity. This revised version was published online in July 2006 with corrections to the Cover Date.     

Microbial conversion of sugars from plant biomass to lactic acid or ethanol

Concerns for our environment and unease with our dependence on foreign oil have renewed interest in converting plant biomass into fuels and 'green' chemicals. The volume of plant matter available makes lignocellulose conversion desirable, although no single isolated organism has been shown to depolymerize lignocellulose and efficiently metabolize the resulting sugars into a specific product. This work reviews selected chemicals and fuels that can be produced from microbial fermentation of plant-derived cell-wall sugars and directed engineering for improvement of microbial biocatalysts. Lactic acid and ethanol production are highlighted, with a focus on engineered Escherichia coli .     

Development of biocatalysts for production of commodity chemicals from lignocellulosic biomass

Lignocellulosic biomass is recognized as potential sustainable source for production of power, biofuels and variety of commodity chemicals which would potentially add economic value to biomass. Recalcitrance nature of biomass is largely responsible for the high cost of its conversion. Therefore, it is necessary to introduce some cost effective pretreatment processes to make the biomass polysaccharides easily amenable to enzymatic attack to release mixed fermentable sugars. Advancement in systemic biology can provide new tools for the development of such biocatalysts for sustainable production of commodity chemicals from biomass. Integration of functional genomics and system biology approaches may generate efficient microbial systems with new metabolic routes for production of commodity chemicals. This paper provides an overview of the challenges that are faced by the processes converting lignocellulosic biomass to commodity chemicals. The critical factors involved in engineering new microbial biocatalysts are also discussed with more emphasis on commodity chemicals.     

Polymers derived from hemicellulosic parts of lignocellulosic biomass

Furfural, which is directly derived from the hemicellulosic parts of lignocellulosic biomass, is considered as one of the most promising platform chemicals to manufacture commodity chemical products such as polymers and their monomers. Its production has already been commercialized. In this review, potentially relevant methods for producing important chemicals from furfural, which are used as monomers for different polymers, and for the polymerization of furfural and its derivatives (e.g., furfuryl alcohol), have been discussed. First, the production of furfural from different lignocellulosic biomasses is presented. Next, the synthesis of various monomers and their highest available yields from furfural are discussed. The polymers that can be directly produced from furfural and its derivatives are explored. Finally, the challenges of producing furfural-based products have been highlighted.

     

New approaches to the chemical control of arthropod pests of livestock

Chemicals are important tools in our effort to control livestock ectoparasites, and they are likely to remain so in the foreseeable future. Chemical control is the most widely used and in most cases the only method available to the producer. Therefore, it is imperative that we continue to seek new chemicals as well as new systems for delivery of those chemicals in an effective, efficient, and safe manner.New approaches to chemical control involve both new chemicals and new delivery systems in a complementary and often a synergistic relationship. Three relatively new classes of chemicals, pyrethroids, insect growth regulators, and avermectins, have provided special opportunities for development of new delivery systems.The development of the insecticidal ear tag has been perhaps the most significant new approach to chemical control of livestock ectoparasites in recent years. Although originally developed for control of ear ticks, the tag has had its greatest impact on control of the horn fly, a major pest of cattle in the U.S. The pyrethroid tags provided season-long control of horn flies in most climates and at the same time dramatically reduced the use of pesticide. Unfortunately, the problem of resistance to pyrethroids in the tags has been encountered. Unless effective techniques for resistance management can be developed, the producer may lose this valuable new tool.Sustained-release boluses provide a means of delivering IGR's, such as methoprene and diflubenzuron, for control of immature stages of the horn fly and face fly in manure of cattle. These devices are designed to lodge in the reticulum of cattle and release the chemical to the digestive tract over an extended period. Bolus formulations may in fact provide a tool for management of horn fly resistance to pyrethroids.Ivermectin, a potent new chemical from a new class of agricultural pesticides, provides an important opportunity for developing innovative delivery systems for control of livestock pests. Its systemic activity against ticks and blood-sucking flies at extremely low dosages provides potential for development of long-lasting subcutaneous implants. Its ability to control immature stages of dung-breeding flies, such as the horn fly and face fly, offers the potential for development of sustained-release boluses for larvicidal treatments.These three selected examples of new approaches to chemical control of livestock ectoparasites point to two obvious trends: 1) reduction in quantity of a chemical to be applied without sacrifice of efficacy and 2) use of controlled-release technology to prolong effectiveness of the chemical. Although the examples presented are focused on applications to cattle, similar approaches have application for other livestock. New approaches such as these have important implications in implementation of either area-wide or IPM control programs. Such programs will need convenient and effective chemical delivery systems to be successful if in fact chemicals are to be a part of the programs.     

Biorefining of biomass to liquid fuels and organic chemicals

The production of liquid and gaseous fuels and industrial chemicals from selected biomass by a process known as biorefining is reviewed. Four broad categories of biomass appear to be suitable feedstocks: woody biomass and forest residues, agricultural residues, directly fermentable crop-grown biomass, and municipal solid waste and sewage sludge. Through the development of suppressed methane fermentation techniques, it is possible to produce valuable organic chemicals such as acetic acid and ethyl acetate, and liquid fuel (rather than fuel gas) by exercising various processing alternatives. Thus the entire field of methane fermentation has been broadened. In the petroleum refining industry, it is usually desirable to produce from crude oil an optimal mixture of industrial organic chemicals and fuels, a concept known as coproduction. The biorefining process reviewed appears to be adaptable to this same concept of coproduction using biomass as a feedstock.     

Advances in thermochemical conversion of woody biomass to energy,fuels and chemicals

Biomass has been recognised as a promising resource for future energy and fuels. The biomass, originated from plants, is renewable and application of its derived energy and fuels is close to carbon-neutral by considering that the growing plants absorb CO₂ for photosynthesis. However, the complex physical structure and chemical composition of the biomass significantly hinder its conversion to gaseous and liquid fuels.This paper reviews recent advances in biomass thermochemical conversion technologies for energy, liquid fuels and chemicals. Combustion process produces heat or heat and power from the biomass through oxidation reactions; however, this is a mature technology and has been successfully applied in industry. Therefore, this review will focus on the remaining three thermochemical processes, namely biomass pyrolysis, biomass thermal liquefaction and biomass gasification. For biomass pyrolysis, biomass pretreatment and application of catalysts can simplify the bio-oil composition and retain high yield. In biomass liquefaction, application of appropriate solvents and catalysts improves the liquid product quality and yield. Gaseous product from biomass gasification is relatively simple and can be further processed for useful products. Dual fluidised bed (DFB) gasification technology using steam as gasification agent provides an opportunity for achieving high hydrogen content and CO₂ capture with application of appropriate catalytic bed materials. In addition, multi-staged gasification technology, and integrated biomass pyrolysis and gasification as well as gasification for poly-generation have attracted increasing attention.     

Woody biomass: Niche position as a source of sustainable renewable chemicals and energy and kinetics of hot-water extraction/hydrolysis

The conversion of biomass to chemicals and energy is imperative to sustaining our way of life as known to us today. Fossil chemical and energy sources are traditionally regarded as wastes from a distant past. Petroleum, natural gas, and coal are not being regenerated in a sustainable manner. However, biomass sources such as algae, grasses, bushes and forests are continuously being replenished. Woody biomass represents the most abundant and available biomass source. Woody biomass is a reliably sustainable source of chemicals and energy that could be replenished at a rate consistent with our needs. The biorefinery is a concept describing the collection of processes used to convert biomass to chemicals and energy. Woody biomass presents more challenges than cereal grains for conversion to platform chemicals due to its stereochemical structures. Woody biomass can be thought of as comprised of at least four components: extractives, hemicellulose, lignin and cellulose. Each of these four components has a different degree of resistance to chemical, thermal and biological degradation. The biorefinery concept proposed at ESF (State University of New York — College of Environmental Science and Forestry) aims at incremental sequential deconstruction, fractionation/conversion of woody biomass to achieve efficient separation of major components. The emphasis of this work is on the kinetics of hot-water extraction, filling the gap in the fundamental understanding, linking engineering developments, and completing the first step in the biorefinery processes. This first step removes extractives and hemicellulose fractions from woody biomass. While extractives and hemicellulose are largely removed in the extraction liquor, cellulose and lignin largely remain in the residual woody structure. Xylo-oligomers and acetic acid in the extract are the major components having the greatest potential value for development. Extraction/hydrolysis involves at least 16 general reactions that could be divided into four categories: adsorption of proton onto woody biomass, hydrolysis reactions on the woody biomass surface, dissolution of soluble substances into the extraction liquor, and hydrolysis and dehydration decomposition in the extraction liquor. The extraction/hydrolysis rates are significantly simplified when the reactivity of all the intermonomer bonds are regarded as identical within each macromolecule, and the overall reactivity are identical for all the extractable macromolecules on the surface. A pseudo-first order extraction rate expression has been derived based on concentrations in monomer units. The reaction rate constant is however lower at the beginning of the extraction than that towards the end of the extraction. Furthermore, the H-factor and/or severity factor can be applied to lump the effects of temperature and residence time on the extraction process, at least for short times. This provides a means to control and optimize the performance of the extraction process effectively.     

Alternatives to animal testing in the safety evaluation of products

The conventional method for assessing the safety of products, ranging from pharmaceuticals to agrochemicals, biocides and industrial and household chemicals - including cosmetics - involves determining their toxicological properties by using experimental animals. The aim is to identify any possible adverse effects in humans by using these animal models. Providing safe products is undoubtedly of the utmost importance but, over the last decade or so, this aim has come into conflict with strong public opinion, especially in Europe, against animal testing. Industry, academia and the regulators have worked in partnership to find other ways of evaluating the safety of products, by non-animal testing, or at least by reducing the numbers of animals required and the severity of the tests in which they are used. There is a long way to go before products can be evaluated without any animal studies, and it may be that this laudable aim is an impossible dream. Nevertheless, considerable progress has been made by using a combination of in vitro tests and the prediction of properties based on chemical structure. The aim of this review is to describe these important and worthwhile developments in various areas of toxicological testing, with a focus on the European regulatory framework for general industrial and household chemicals.     

Separation of bio‐based chemicals from fermentation broths by salting‐out extraction

The possibility of creating a biorefinery using inexpensive biomass has attracted a great deal of attention, which is mainly focused on the improvement of strains and fermentation, whereas few resources have been spent on downstream processing. Bio‐based chemical downstream processing can become a bottleneck in industrial production because so many impurities are introduced into the fermentation broth. This review introduces a technique referred to as salting‐out extraction, which is based on the partition difference between chemicals in two phases consisting of salts and polymers or hydrophilic solvents, hydrophobic solvents, and amphipathic chemicals. The effects of solvents and salts on the formation of two phases were discussed, as was the use of this method to recover bio‐based chemicals. This review focused on the separation of hydrophilic chemicals (1,3‐propanediol, 2,3‐butanediol, acetoin, and lactic acid) from fermentation broths. Diols could be recovered at a high yield from fermentation broths without pretreatment especially with a hydrophilic solvent‐based system, whereas the recovery of organic acids was slightly lower. Most of the impurities (cells and proteins) were removed during the same step. Extractive fermentations were also used for polymer‐based aqueous two‐phase systems.     

Development and prevalidation of a list of structure-activity relationship rules to be used in expert systems for prediction of the skin-sensitising properties of chemicals

The new European Union (EU) chemicals policy, as described in the White Paper entitled Strategy for a Future Chemicals Policy, has identified a need for computer-based tools suitable for predicting the hazardous properties of chemicals. Two sets of structural alerts (fragments of chemical structure) for the prediction of skin sensitisation hazard classification ("R43, may cause sensitisation by skin contact") have been drawn up, based on sensitising chemicals from a regulatory database (containing data for the EU notification of new chemicals). These alerts comprise 15 rules for chemical structures deemed to be sensitising by direct action of the chemicals with cells or proteins within the skin, and three rules for substructures that act indirectly, i.e. requiring chemical or biochemical transformation. The predictivity rates of the rules were found to be good (positive predictivity, 88%; false-positive rate, 1%; specificity, 99%; negative predictivity, 74%; false-negative rate, 80%; sensitivity, 20%). Because of the confidential nature of the regulatory database, the rules are supported by examples of sensitising chemicals taken from the "Allergenliste" now held by the Federal Institute for Risk Assessment (BfR) and the DEREK for Windows expert system. The rules were prevalidated against data not used for their development. As a result of the prevalidation study, it is proposed that the two sets of structural alerts should be taken forward for formal validation, with a view to incorporating them into regulatory guidelines.     

以端粒酶为靶标抗癌药物筛选模型建立及端粒酶抑制剂筛选

新药研究与开发离不开筛选模型 ,而筛选模型的关键是寻找、确定和制备药物筛选靶———药靶 .近来研究表明 ,端粒酶与恶性肿瘤的发生和发展有着密切的关系 ,端粒酶在恶性肿瘤细胞中表达率占80 %～ 90 % ,而在正常体细胞中不表达[1～ 4 ] .这表明端粒酶在维持肿瘤细胞的增殖中起着重要作用 .抑制端粒酶的活性有可能抑制肿瘤的生长 ,因而端粒酶被认为是恶性肿瘤诊断和治疗的新靶标 .以端粒酶为抗癌药物作用的靶标 ,建立抗癌药物筛选模型 ,在分子水平上筛选针对端粒酶的抑制剂 ,进而获得特异性高、针对性强、毒副作用小的新型广谱的抗癌药物 ,…     

New approaches to the chemical synthesis of bioactive oligosaccharides.

The past year has seen some major advances in the area of carbohydrate synthesis using chemical methods. Progress in all areas of synthetic methodology, including new protecting groups and coupling methods, has been reported. A number of complex carbohydrate structures have been prepared using known, as well as new, methods. The goal to allow nonspecialists access to defined carbohydrate structures for biochemical, biophysical and biological studies has drawn closer by the introduction of two approaches towards synthesis automation. A one-pot glycosylation strategy utilized computer-assisted synthesis planning and the first solid-phase automated synthesizer was introduced very recently.     

Light-energy conversion in engineered microorganisms

Increasing interest in renewable resources by the energy and chemical industries has spurred new technologies both to capture solar energy and to develop biologically derived chemical feedstocks and fuels. Advances in molecular biology and metabolic engineering have provided new insights and techniques for increasing biomass and biohydrogen production, and recent efforts in synthetic biology have demonstrated that complex regulatory and metabolic networks can be designed and engineered in microorganisms. Here, we explore how light-driven processes may be incorporated into nonphotosynthetic microbes to boost metabolic capacity for the production of industrial and fine chemicals. Progress towards the introduction of light-driven proton pumping or anoxygenic photosynthesis into Escherichia coli to increase the efficiency of metabolically-engineered biosynthetic pathways is highlighted.     

A new measure of xenobiotic toxicity to the first-line human defence system from the time-resolved phagocyte luminescence

A new measure of toxicity based on stochastic modelling of single photon-counting processes, representing time-resolved phagocyte luminescence of xenobiotic-perturbed human neutrophils, has been constructed. The stochastic measure of toxicity has been verified by the QSAR method, and then compared and contrasted with the traditional toxicity measure used in bio- and chemiluminescent research. Phenol and benzene homologues were chosen as perturbers due to their importance from the viewpoint of ecotoxicology and occupational medicine.