Trends in the search for bioactive microbial metabolites

Summary Bioactive microbial metabolites are attracting increasing attention as useful agents for medicine, veterinary medicine, agriculture, and as unique biochemical tools. A review of the current trends in the discovery-of new metabolites shows that the number of active compounds with non-antibiotic type of activity has increased, resulting in an expansion of the variety of bioactivity of microbial metabolites. Factors that contribute to the increased rate of discovery include: development of new methods for activity measurement, exploitation of novel groups of microorganisms as sources of active compounds, new directions for chemical modification, and incorporation of newer knowledge of biotechnology into screening systems. To exemplify this, typical screening methods, and chemical and biological properties of several bioactive compounds obtained by these methods are discussed.     

蓖麻生物工程研究进展

蓖麻是一种高蓄能植物和工业原料植物,具有很大的开发利用价值。本文从组织培养和遗传转化两个方面并结合本实验室的工作综述了蓖麻生物工程研究的最新进展。在蓖麻组织培养方面,不同的外植体中以成熟种子的胚轴最适宜,而在不同激素中以TDZ诱导丛生芽的效率最高,并以此为基础建立了蓖麻离体再生体系。在遗传转化方面,不同的转化方法中以农杆菌介导法最适合蓖麻转化。蓖麻胚轴对卡那霉素不敏感,潮霉素是蓖麻转化的适宜筛选剂。文中指出了蓖麻生物工程研究中存在的问题,并对应用生物技术培育蓖麻新品种和促进蓖麻生产的可能性进行了讨论。     

Use of molecular techniques in bioremediation

In a practical sense, biotechnology is concerned with the production of commercial products generated by biological processes. More formally, biotechnology may be defined as "the application of scientific and engineering principles to the processing of material by biological agents to provide goods and services" (Cantor, 2000). From a historical perspective, biotechnology dates back to the time when yeast was first used for beer or wine fermentation, and bacteria were used to make yogurt. In 1972, the birth of recombinant DNA technology moved biotechnology to new heights and led to the establishment of a new industry. Progress in biotechnology has been truly remarkable. Within four years of the discovery of recombinant DNA technology, genetically modified organisms (GMOs) were making human insulin, interferon, and human growth hormone. Now, recombinant DNA technology and its products--GMOs are widely used in environmental biotechnology (Glick and Pasternak, 1988; Cowan, 2000). Bioremediation is one of the most rapidly growing areas of environmental biotechnology. Use of bioremediation for environmental clean up is popular due to low costs and its public acceptability. Indeed, bioremediation stands to benefit greatly and advance even more rapidly with the adoption of molecular techniques developed originally for other areas of biotechnology. The 1990s was the decade of molecular microbial ecology (time of using molecular techniques in environmental biotechnology). Adoption of these molecular techniques made scientists realize that microbial populations in the natural environments are much more diverse than previously thought using traditional culture methods. Using molecular ecological methods, such as direct DNA isolation from environmental samples, denaturing gradient gel electrophoresis (DGGE), PCR methods, nucleic acid hybridization etc., we can now study microbial consortia relevant to pollutant degradation in the environment. These techniques promise to provide a better understanding and better control of environmental biotechnology processes, thus enabling more cost effective and efficient bioremediation of our toxic waste and contaminated environments.     

Relevance of microbial coculture fermentations in biotechnology

The purpose of this article is to review coculture fermentations in industrial biotechnology. Examples for the advantageous utilization of cocultures instead of single cultivations include the production of bulk chemicals, enzymes, food additives, antimicrobial substances and microbial fuel cells. Coculture fermentations may result in increased yield, improved control of product qualities and the possibility of utilizing cheaper substrates. Cocultivation of different micro‐organisms may also help to identify and develop new biotechnological substances. The relevance of coculture fermentations and the potential of improving existing processes as well as the production of new chemical compounds in industrial biotechnology are pointed out here by means of more than 35 examples.     

Microbial production of riboflavin: Biotechnological advances and perspectives

Riboflavin is an essential nutrient for humans and animals, and its derivatives flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) are cofactors in the cells. Therefore, riboflavin and its derivatives are widely used in the food, pharmaceutical, nutraceutical and cosmetic industries. Advances in biotechnology have led to a complete shift in the commercial production of riboflavin from chemical synthesis to microbial fermentation. In this review, we provide a comprehensive review of biotechnologies that enhance riboflavin production in microorganisms, as well as representative examples. Firstly, the synthesis pathways and metabolic regulatory processes of riboflavin in microorganisms; and the current strategies and methods of metabolic engineering for riboflavin production are systematically summarized and compared. Secondly, the using of systematic metabolic engineering strategies to enhance riboflavin production is discussed, including laboratory evolution, histological analysis and high-throughput screening. Finally, the challenges for efficient microbial production of riboflavin and the strategies to overcome these challenges are prospected.     

Microbial steroid transformations: current state and prospects

Studies of steroid modifications catalyzed by microbial whole cells represent a well-established research area in white biotechnology. Still, advances over the last decade in genetic and metabolic engineering, whole-cell biocatalysis in non-conventional media, and process monitoring raised research in this field to a new level. This review summarizes the data on microbial steroid conversion obtained since 2003. The key reactions of structural steroid functionalization by microorganisms are highlighted including sterol side-chain degradation, hydroxylation at various positions of the steroid core, and redox reactions. We also describe methods for enhancement of bioprocess productivity, selectivity of target reactions, and application of microbial transformations for production of valuable pharmaceutical ingredients and precursors. Challenges and prospects of whole-cell biocatalysis applications in steroid industry are discussed.     

The Earth's bounty: assessing and accessing soil microbial diversity.

The study of microbial diversity represents a major opportunity for advances in biology and biotechnology. Recent progress in molecular microbial ecology shows that the extent of microbial diversity in nature is far greater than previously thought. Here, we discuss methods to analyse microorganisms from natural environments without culturing them and new approaches for gaining access to the genetic and chemical resources of these microorganisms.     

发酵中药--拓展中药新药研究开发的新空间

发酵中药是现代生物技术和中药研究的完美结合,依靠微生物发酵来生产发酵中药近来正逐渐成为研究的热点,并为中药的发展开辟了新空间。本文综述了发酵中药的应用历史及现况、作用机理、优势特色和发展方向。     

Small bugs, big business: the economic power of the microbe

The versatility of microbial biosynthesis is enormous. The most industrially important primary metabolites are the amino acids, nucleotides, vitamins, solvents, and organic acids. Millions of tons of amino acids are produced each year with a total multibillion dollar market. Many synthetic vitamin production processes are being replaced by microbial fermentations. In addition to the multiple reaction sequences of fermentations, microorganisms are extremely useful in carrying out biotransformation processes. These are becoming essential to the fine chemical industry in the production of single-isomer intermediates. Microbially produced secondary metabolites are extremely important to our health and nutrition. As a group, they have tremendous economic importance. The antibiotic market amounts to almost 30 billion dollars and includes about 160 antibiotics and derivatives such as the beta-lactam peptide antibiotics, the macrolide polyketide erythromycin, tetracyclines, aminoglycosides and others. Other important pharmaceutical products produced by microrganisms are hypocholesterolemic agents, enzyme inhibitors, immunosuppressants and antitumor compounds, some having markets of over 1 billion dollars per year. Agriculturally important secondary metabolites include coccidiostats, animal growth promotants, antihelmintics and biopesticides. The modern biotechnology industry has made a major impact in the business world, biopharmaceuticals (recombinant protein drugs, vaccines and monoclonal antibodies) having a market of 15 billion dollars. Recombinant DNA technology has also produced a revolution in agriculture and has markedly increased markets for microbial enzymes. Molecular manipulations have been added to mutational techniques as means of increasing titers and yields of microbial procresses and in discovery of new drugs. Today, microbiology is a major participant in global industry. The best is yet to come as microbes move into the environmental and energy sectors.     

Aspergillus as a multi-purpose cell factory: current status and perspectives

Aspergilli have a long history in biotechnology as expression platforms for the production of food ingredients, pharmaceuticals and enzymes. The achievements made during the last years, however, have the potential to revolutionize Aspergillus biotechnology and to assure Aspergillus a dominant place among microbial cell factories. This mini-review will highlight most recent breakthroughs in fundamental and applied Aspergillus research with a focus on new molecular tools, techniques and products. New trends and concepts related to Aspergillus genomics and systems biology will be discussed as well as the challenges that have to be met to integrate omics data with metabolic engineering attempts.     

Safe biotechnology. Part 6. Safety assessment,in respect of human health,of microorganisms used in biotechnology

The assessment of microorganisms in respect to human health is an important step for the introduction of new natural and genetically modified production strains to biotechnology. This report outlines the potential hazards posed by industrial microorganisms, important considerations related to pathogenicity, such as routes and portals of entry into the human body, mechanisms of spread of biological material and a definition of pathogenicity.Furthermore the most important steps in the assessment of pathogenicity of unknown strains are described. A short overview on characterization and in vitro and in vivo tests is presented. The hazard related to allergens and toxic metabolites is reviewed and the choice of methods and the handling of strains with unknown potential are discussed.     

Advances in microbial biotechnology of bile acids

The recent advances in microbial biotechnology of production of bile acid metabolites helped to identify a number of neutral and acidic steroidal compounds useful as drugs and drug intermediates on a scale which would not have been possible by classical chemical transformations. Microbial transformations viz., hydroxylation, dehydroxylation, reduction of the carbonyl moieties, epimerization, side-chain metabolism, introduction of carbon-carbon double bonds into the steroid nucleus, deconjugation of bile acid conjugates carried out by various microorganisms for production of useful metabolites with special reference to newer techniques including cell immobilization and transposon mutagenesis for selective transformations are reviewed. The different pathways of microbial degradation of bile acids leading to the formation of various products are discussed. A compilation of the metabolites formed by various microorganisms from the bile acids or their conjugates and reported during the period 1979-1992 is also provided.     

Metagenomics,biotechnology with non-culturable microbes

Metagenomics as a new field of research has been developed over the past decade to elucidate the genomes of the non-cultured microbes with the goal to better understand global microbial ecology on the one side, and on the other side it has been driven by the increasing biotechnological demands for novel enzymes and biomolecules. Since it is well accepted that the majority of all microbes has not yet been cultured, the not-yet-cultivated microbes represent a shear unlimited and intriguing resource for the development of novel genes, enzymes and chemical compounds for use in biotechnology. However, with respect to biotechnology, metagenomics faces now two major challenges. Firstly, it has to identify truly novel biocatalysts to fulfil the needs of industrial processes and green chemistry. Secondly, the already available genes and enzymes need to be implemented in production processes to further prove the value of metagenome-derived sequences.     

Maßgeschneiderte Mikroorganismen

Tailor‐made microorganisms Microbial diversity provides unlimited resources for the development of novel industrial processes and products. Since the beginning of the 20th century microorganisms have been successfully applied for the large scale production of bio‐based products. In recent years, modern methods of strain development and Synthetic Biology have enabled biotech engineers to design even more sophisticated and tailor‐made microorganisms. These microbes serve industrial processes for the production of bulk chemicals, enzymes, polymers, biofuels as well as plant‐derived ingredients such as Artemisinin in an ecologically and economically sustainable and attractive fashion. In the future, production of advanced biofuels, microbial fuel cells, CO₂ as feedstock and microbial cellulose are research topics as well as challenges of global importance. Continuous efforts in microbiology and biotechnology research will be pivotal for white biotechnology to gain more momentum in transforming the chemical industry towards a knowledge based bio‐economy.     

Success evaluation of the biological control of Fusarium wilts of cucumber,banana, and tomato since 2000 and future research strategies

The Fusarium wilt caused by Fusarium oxysporum strains is the most devastating disease of cucumber, banana, and tomato. The biological control of this disease has become an attractive alternative to the chemical fungicides and other conventional control methods. In this review, the research trends and biological control efficiencies (BCE) of different microbial strains since 2000 are reviewed in detail, considering types of microbial genera, inoculum application methods, plant growth medium and conditions, inoculum application with amendments, and co-inoculation of different microbial strains and how those affect the BCE of Fusarium wilt. The data evaluation showed that the BCE of biocontrol agents was higher against the Fusarium wilt of cucumber compared to the Fusarium wilts of banana and tomato. Several biocontrol agents mainly Bacillus, Trichoderma, Pseudomonas, nonpathogenic Fusarium, and Penicillium strains were evaluated to control Fusarium wilt, but still this lethal disease could not be controlled completely. We have discussed different reasons of inconsistent results and recommendations for the betterment of BCE in the future. This review provides knowledge of the biotechnology of biological control of Fusarium wilt of cucumber, banana, and tomato in a nut shell that will provide researchers a beginning line to start and to organize and plan research for the future studies.     

Microalgae as source of biofuel,food, fodder,and medicines

Current status and future prospects of such problem as the production of microalgae and their application for biofuel generation (biodiesel, biohydrogen, bioethanol), as well as other products, is discussed in the review. The use of microalgae in human food, fodder, cosmetics, dyes, polysaccharides, antioxidants, medicines, and other products is quite promising. Presently, microalgae are noncompetitive with plant materials, due to economic reasons, in serving as a source of biofuel. Thereby, it is urgently necessary in modern biotechnology to improve the methods for the production of microalgae and search for new ways of their processing.     

Synthetic microbial ecosystems for biotechnology

Most highly controlled and specific applications of microorganisms in biotechnology involve pure cultures. Maintaining single strain cultures is important for industry as contaminants can reduce productivity and lead to longer “down-times” during sterilisation. However, microbes working together provide distinct advantages over pure cultures. They can undertake more metabolically complex tasks, improve efficiency and even expand applications to open systems. By combining rapidly advancing technologies with ecological theory, the use of microbial ecosystems in biotechnology will inevitably increase. This review provides insight into the use of synthetic microbial communities in biotechnology by applying the engineering paradigm of measure, model, manipulate and manufacture, and illustrate the emerging wider potential of the synthetic ecology field. Systems to improve biofuel production using microalgae are also discussed.     

Recent advances in plant biotechnology and genetic engineering for production of secondary metabolites

For a long time people are using plants not only as crop cultures but also for obtaining of various chemicals. Currently plants remain one of the most important and essential sources of biologically active compounds in spite of progress in chemical or microbial synthesis. In our review we compare potentials and perspectives of modern genetic engineering approaches for pharmaceutical biotechnology and give examples of actual biotechnological systems used for production of several promising natural compounds: artemisinin, paclitaxel and scopolamine.     

Polymer and sprinkler droplet energy effects on sugar beet emergence, soil penetration resistance, and aggregate stability

The rapid development of agricultural biotechnology and release of new transgenic plants for agriculture has provided many economic benefits, but has also raised concern over the potential impact of transgenic plants on the environment. Considerable research has now been conducted on the effects of transgenic plants on soil microorganisms. These effects include unintentional changes in the chemical compositions of root exudates, and the direct effects of transgenic proteins on nontarget species of soil microorganisms. Most studies to date suggest that transgenic plants that have been released cause minor changes in microbial community structures that are often transient in duration. However, due to our limited knowledge of the linkage between microbial community structure and function, more work needs to be done on a case-by-case basis to further evaluate the effects of transgenic plants on soil microorganisms and soil ecosystem functions. This review summarizes the results of a variety of experiments that have been conducted to specifically test the effects of transgenic plants on soil microorganisms, and particularly examines the types of methods that are being used to study microbial interactions with transgenic plants.     

The roots—a short history of industrial microbiology and biotechnology

Early biotechnology (BT) had its roots in fascinating discoveries, such as yeast as living matter being responsible for the fermentation of beer and wine. Serious controversies arose between vitalists and chemists, resulting in the reversal of theories and paradigms, but prompting continuing research and progress. Pasteur’s work led to the establishment of the science of microbiology by developing pure monoculture in sterile medium, and together with the work of Robert Koch to the recognition that a single pathogenic organism is the causative agent for a particular disease. Pasteur also achieved innovations for industrial processes of high economic relevance, including beer, wine and alcohol. Several decades later Buchner, disproved the hypothesis that processes in living cells required a metaphysical ‘vis vitalis’ in addition to pure chemical laws. Enzymes were shown to be the chemical basis of bioconversions. Studies on the formation of products in microbial fermentations, resulted in the manufacture of citric acid, and chemical components required for explosives particularly in war time, acetone and butanol, and further products through fermentation. The requirements for penicillin during the Second World War lead to the industrial manufacture of penicillin, and to the era of antibiotics with further antibiotics, like streptomycin, becoming available. This was followed by a new class of high value-added products, mainly secondary metabolites, e.g. steroids obtained by biotransformation. By the mid-twentieth century, biotechnology was becoming an accepted specialty with courses being established in the life sciences departments of several universities. Starting in the 1970s and 1980s, BT gained the attention of governmental agencies in Germany, the UK, Japan, the USA, and others as a field of innovative potential and economic growth, leading to expansion of the field. Basic research in Biochemistry and Molecular Biology dramatically widened the field of life sciences and at the same time unified them considerably by the study of genes and their relatedness throughout the evolutionary process. The scope of accessible products and services expanded significantly. Economic input accelerated research and development, by encouraging and financing the development of new methods, tools, machines and the foundation of new companies. The discipline of ‘New Biotechnology’ became one of the lead sciences. Although biotechnology has historical roots, it continues to influence diverse industrial fields of activity, including food, feed and other commodities, for example polymer manufacture, biofuels and energy production, providing services such as environmental protection, and the development and production of many of the most effective drugs. The understanding of biology down to the molecular level opens the way to create novel products and efficient environmentally acceptable methods for their production.