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PubMed2026

Cross-Kingdom Siderophores: Biosynthesis, Ecology, and Biotechnological Applications.

Microbial siderophores are high-affinity iron-binding compounds which are produced by bacteria, fungi, and actinomycetes to obtain iron and survive and interact with different species in an iron-deficient environment. While the conventional research on siderophore systems deals mainly with the study within the same taxa, modern researchers have increased their inclination toward cross-kingdom integration of siderophore behavior and their impact on host-associated environments. This can be largely attributed to differences in biosynthetic gene clusters, receptor systems, and regulatory networks, which produce distinct genotype-to-phenotype results determining microbial cooperation and competition. Current advancements in genomic research, together with omics studies like transcriptomics, proteomics, and metabolomics, have created newer insights into how siderophores function. However, the present literature evidences multiple major gaps in multi-omics data because the link between genomes and metabolomes remains weak due to inconsistent regulatory data sets and failure in identifying producer-consumer relationships in polymicrobial systems. Additionally, major constraints like molecular instability, delivery system limitations, host toxicity, limitations in upscaling, and regulatory issues delimit the use of siderophores in medical treatment, agricultural practices, and environmental biotechnology. This review aims to bridge the existing knowledge about siderophore biochemistry, biosynthesis, ecological functions, and genetic regulation across kingdoms while integrating multi-omics outlook with translational considerations. Thus, by connecting molecular mechanisms with evolutionary cross-talk, this study aims to provide a system-level framework in the world of siderophore-mediated iron uptake and therefore shapes future directions in emerging fields of microbial engineering, precision therapies, and sustainable biotechnology.

Fur regulation↗
PubMed1992

Production of vitamins, coenzymes and related biochemicals by biotechnological processes.

Vitamins and related biofactors belong to those few chemicals with a direct positive appeal to people. There is indeed a large need for extra vitamins, other than those derived from plant and animal food sources, due to unbalanced food habits or processing, food shortage or disease. Added vitamins are now either prepared chemically or biotechnologically via fermentation or bioconversion processes. Several vitamins and related biofactors are now only or mainly produced chemically (vitamin A, cholecalciferol (D3), tocopherol (E), vitamin K2, thiamine (B1), niacin (PP or B3), pantothenic acid (B5), pyridoxine (B6), biotin (H or B8), folic acid (B9) or via extraction processes (beta-carotene or provitamin A, provitamin D3, tocopherol, vitamin F-group). However, for several of these compounds microbiological or algal methods also exist or are rapidly emerging. Others are produced practically exclusively via fermentation (ergosterol or provitamin D2, riboflavin (B2), cyanocobalamin (B12), orotic acid (B13), vitamin F-group, ATP, nucleosides, coenzymes, etc. or via microalgal culture (beta-carotene, E, F). Both chemical and microbial processes are run industrially for vitamin B2 while vitamin C (ascorbic acid) is produced via a combination of chemical reactions and fermentation processes. A survey is given here of the current state of vitamin production, with emphasis on developments and strategies for improved biotechnological production and its significance, as compared to existing chemical processes. The screening or construction of vitamin hyperproducing microbial strains is a difficult task; pathway elucidation and metabolic (de)regulation need further study; r-DNA technology has only recently been introduced; improved fermentation processes and immobilised biocatalysts bioconversions for the synthesis of chiral vitamin compounds or intermediates or derivatives are gaining importance; the recovery and purification of these vitamin compounds from their fermentation broths remains equally complex.

Biotechnology↗
PubMed2004

Pharmacokinetic aspects of biotechnology products.

In recent years, biotechnologically derived peptide and protein-based drugs have developed into mainstream therapeutic agents. Peptide and protein drugs now constitute a substantial portion of the compounds under preclinical and clinical development in the global pharmaceutical industry. Pharmacokinetic and exposure/response evaluations for peptide and protein therapeutics are frequently complicated by their similarity to endogenous peptides and proteins as well as protein nutrients. The first challenge frequently comes from a lack of sophistication in various analytical techniques for the quantification of peptide and protein drugs in biological matrices. However, advancements in bioassays and immunoassays--along with a newer generation of mass spectrometry-based techniques--can often provide capabilities for both efficient and reliable detection. Selection of the most appropriate route of administration for biotech drugs requires comprehensive knowledge of their absorption characteristics beyond physicochemical properties, including chemical and metabolic stability at the absorption site, immunoreactivity, passage through biomembranes, and active uptake and exsorption processes. Various distribution properties dictate whether peptide and protein therapeutics can reach optimum target site exposure to exert the intended pharmacological response. This poses a potential problem, especially for large protein drugs, with their typically limited distribution space. Binding phenomena and receptor-mediated cellular uptake may further complicate this issue. Elimination processes--a critical determinant for the drug's systemic exposure--may follow a combination of numerous pathways, including renal and hepatic metabolism routes as well as generalized proteolysis and receptor-mediated endocytosis. Pharmacokinetic/pharmacodynamic (PK/PD) correlations for peptide and protein-based drugs are frequently convoluted by their close interaction with endogenous substances and physiologic regulatory feedback mechanisms. Extensive use of pharmacokinetic and exposure/response concepts in all phases of drug development has in the past been identified as a crucial factor for the success of a scientifically driven, evidence-based, and thus accelerated drug development process. Thus, PK/PD concepts are likely to continue and expand their role as a fundamental factor in the successful development of biotechnologically derived drug products in the future.

Animals↗
PubMed2006

Debaryomyces hansenii--an extremophilic yeast with biotechnological potential.

We illuminate the ecological, physiological and genetic characteristics of the yeast Debaryomyces hansenii in the view of our belief that this metabolically versatile, non-pathogenic, osmotolerant and oleaginous microorganism represents an attractive target for fundamental and applied biotechnological research. To this end, we give a broad overview of extant biotechnological procedures using D. hansenii, e.g. in the manufacture of various foods, and propose research into the heterologous synthesis of a range of fine chemicals.

Biotechnology↗
PubMedDate not supplied

HAP-Like CCAAT-binding complexes in filamentous fungi: implications for biotechnology.

Regulatory CCAAT boxes are found frequently in eukaryotic promoter regions. They are bound by different CCAAT-binding factors. Until now, a single CCAAT-binding complex has been reported in fungi. It is also found in higher eukaryotes and is highly conserved among eukaryotic organisms. This multimeric protein complex is designated HAP, AnCF, CBF, or NF-Y. The complex consists of at least three subunits. In fungi, only the HAP complex of Saccharomyces cerevisiae had been known for a long time. The recent cloning of genes encoding the components of the corresponding complex (AnCF/PENR1) of Aspergillus nidulans and characterization of CCAAT-regulated genes in A. nidulans, as well as other filamentous fungi, led to a deeper insight into the role of this transcription complex, in particular in aerobically growing fungi. An overview of the function of HAP-like complexes in gene regulation in filamentous fungi is presented. Some of the genes that have been found to be regulated by HAP-like complexes encode enzymes of biotechnological interest, like taka-amylase, xylanases, cellobiohydrolase, and penicillin biosynthesis enzymes. The importance of HAP-like complexes in controlling the expression of biotechnologically important genes is discussed.

Biotechnology↗
PubMed1999

Use and limitations of modular metabolic control analysis in medicine and biotechnology.

By Metabolic Control Analysis (MCA), it has been shown that control on flux is in most cases shared by several enzymes rather than concentrated on one "rate-limiting step." This analysis also allows the quantification of the control exerted by groups (modules) of enzymes. The modules may correspond to spatial compartments or to functional units. A brief outline of the modular approach to MCA is given. The criteria by which the system can be modularized and the concept of monofunctional unit are explained. Various studies in which control analysis was applied to biotechnological and medical issues are reviewed. In particular, MCA has turned out to be helpful in the assessment of the severity of enzyme deficiencies. Another application is the search for target enzymes or enzyme groups where pharmaceuticals can suppress the metabolism of pathogenic microorganisms most. In biotechnology, modular and "traditional" control analyses are valuable tools for choosing the most promising targets for genetic manipulation so as to increase a biosynthetic flux. As control coefficients are linear approximations, the effect of enhancing the activities of enzymes to a larger extent is often overestimated. Further limitations such as the restriction to stationary states, uncertainties due to spatial heterogeneities and the impact of experimental error are discussed.

Animals↗
PubMed2000

Canadian biotechnology start-ups, 1991-1997: the role of incumbents' patents and strategic alliances in controlling competition.

Fligstein (1996) contends that organizations act to exploit the institutional context in which they are embedded so as to stabilize the competition they face. Drawing on Fligstein's theoretical analysis, we conceptualize incumbent biotechnology firms' patent-ing and alliance-building activities as attempts to stabilize and control potential competition and analyze how these activities shape rates of founding in the Canadian biotechnology industry. We find that increases in the level and concentration of incumbents' patenting discourage founding, particularly in human application sectors of the industry where development and approval processes are more costly and time consuming. Incumbents' horizontal alliances depress start-ups; vertical alliances stimulate start-ups. Our findings highlight how technology appropriation and strategic alliances structure the competitive dynamics and evolution of high-technology, knowledge-intensive industries.

Biotechnology↗
PubMed2003

Plant molecular biology and biotechnology research in the post-recombinant DNA era.

After the beginning of the recombinant DNA era in the mid-1970s, researchers in India started to make use of the new technology to understand the structure of plant genes and regulation of their expression. The outcome started to appear in print in early the 1980s and genes for histones, tubulin, photosynthetic membrane proteins, phototransduction components, organelles and those regulated differentially by developmental and extrinsic signals were sequenced and characterized. Some genes of biotechnological importance like those encoding an interesting seed protein and the enzyme glyoxalase were also isolated. While work on the characterization of genome structure and organization was started quite early, it remained largely focused on the identification of DNA markers and genetic variability. In this context, the work on mustard, rice and wheat is worth mentioning. In the year 2000, India became a member of the international consortium to sequence entire rice genome. Several laboratories have also given attention to regulated expression of plastid and nuclear genes as well as to isolate target-specific promoters or design promoters with improved potential. Simultaneously, transgenic systems for crops like mustard, rice, wheat, cotton, legumes and several vegetables have been established. More recently, genes of agronomic importance like those for insect resistance, abiotic stress tolerance, nutritional improvement and male sterility, isolated in India or abroad, have been utilized for raising transgenics for crop improvement. Some of these transgenics have already shown their potential in containment facility or limited field trials conducted under the stipulated guidelines. Plant molecular biology and biotechnology are thus clearly poised to make an impact on research in basic biology and agriculture in the near future.

Agriculture↗
PubMed2000

Development of applied microbiology to modern biotechnology in Japan.

Development of modern biotechnology in Japan is characterized by unique contributions from applied microbiology and bioindustry. This review tries to summarize these original contributions with special emphasis on industrial production of useful substances by microorganisms. In the first part, development of applied microbiology and bioindustry in the last half of the twentieth century is summarized with a brief overview of the traditional background. In the second part, recent progress is reviewed with citation of typical achievements in biotechnology, applied enzymology, secondary metabolites, genetic engineering, and screening of microbial diversity, respectively.

Amino Acids↗
PubMed2000

Biotechnology in Switzerland and a glance at Germany.

The roots of biotechnology go back to classic fermentation processes, which starting from spontaneous reactions were developed by simple means. The discovery of antibiotics made contamination-free bioprocess engineering indispensable, which led to a further step in technology development. On-line analytics and the use of computers were the basis of automation and the increase in quality. On both sides of the Atlantic, molecular biology emerged at the same time, which gave genetic engineering in medicine, agriculture, industry and environment new opportunities. The story of this new advanced technology in Switzerland, with a quick glance at Germany, is followed back to the post-war years. The growth of research and teaching and the foundation of the European Federation of Biotechnology (EFB) are dealt with. The promising phase of the 1960s and 1970s soon had to give way to a restrictive policy of insecurity and anxiousness, which, today, manifests itself in the rather insignificant contributions of many European countries to the new sciences of genomics, proteomics and bioinformatics, as well as in the resistance to the use of transgenic agricultural crops and their products in foods.

Agriculture↗
PubMed1987

Stock-taking concerning international activities in the field of biotechnology. A basis for research policy decisions.

The objective selection of biotechnological priority areas in accordance with global goals established by the government, which is undertaken jointly by science, industry and the government, poses some problems. In order to objectify decisions, therefore, a data recording system has been developed by way of example (for the field of biotechnology in Japan), which enables an analysis to be made of research activities to date as well as forecasts of the future development.

Biotechnology↗
PubMed1987

Biotechnology in Japan and other Asian countries. A computer-based approach to continuous assessment.

By combining information about Biotechnology in Japan manually retrieved from Chemical Abstracts (Biochemical Section) with information obtained from Japanese sources, Japanese scientific meetings and from appropriate magazines such as Nikkei Biotech, a basis was formed for a better understanding of the status and perspectives of this field. Through the development of a "biotechnology abstract analyzer" program, these data were further refined and prepared for continuous up-date. Thus, assessment of changes in institute structures and trends in research goals became possible. It is evident that similar procedures can be applied to any field of science in other geographic areas.

Asia↗
PubMed1993

Regulatory affairs and biotechnology in Europe: III. Introduction into good regulatory practice--validation of virus removal and inactivation.

This paper provides for an overview on the practical consequences of the EC guideline (III/8115/89): Validation of Virus Removal and Inactivation. This guideline can only be used as a blueprint in combination with other specific guidelines, especially those concerned with EC recommendations during production and quality control for various biotech products. A potential risk associated with the production and use of biological products is viral contamination. This contamination may be present in the source material, eg. human blood, human or animal tissues, cell banks, or introduced in the manufacturing process through the use of animal sera (eg. foetal calf serum or trypsin) in cell culture supernatant. The objectives of validation are to establish--ideally both qualitatively as well as quantitatively--the overall level of virus clearance. Evidence of viral clearance must be obtained in all stages of purification and adequate viral removal and/or inactivation must be proven. The method used when validating viral removal and/or inactivation is by challenging the system through the deliberate addition ("spiking") of significant amounts of virus into the crude material to be purified and to different fractions obtained during the various purification stages. Removal or inactivation of the virus during the subsequent stages of purification and/or inactivation is thereafter determined. Such a quality system is by no means a simple one: it is estimated that in some production lines around 600 Standard Operating Procedures are necessary to guarantee the quality and the safety of the desired biotechnological product. Small companies will probably not be able to perform all procedures needed for obtaining the desired quality of the product. Then, external laboratories may take over a part of the Part II development requirements, which may not be representative for the total of internal Quality Assurance. New developments in the production and quality control of biotechnological products may require that companies should introduce novel, sophisticated methods such as: polymerase chain reaction (PCR), as yet not recommended by the CPMP in detail.

Animals↗
PubMed1989

Regulatory affairs and biotechnology in Europe. II. The CPMP, "High Tech" and Multi-State procedures.

This paper describes the EEC regulatory requirements for the preparation and execution of a community concertation "High Tech" procedure and compares this "High Tech" procedure with the Multi-State procedure. According to a decision of the European Commission enforced in July 1987, medicinal products, derived from high technology methods have been grouped in two categories: A. and B. Category A. concerns biotechnology products made by R-DNA techniques and by manipulation of mammalian cells. Category B. comprises all other products made by high technology. Before applying for an EEC marketing licence (e.g. submission for registration) one must ascertain whether a product is most appropriate in Category A. or B. and one should contact a licencing authority at an early stage to discuss the planned submission. Various procedures for submission have to be followed: 1. for the so-called "High Tech" products and especially products derived from biotechnology with therapeutic applications (Category A.), it is mandatory that one of the Member States accepts the submission. 2. The "High Tech" procedure is derived from the so-called "2-country" (Multi-State) procedure, in which for the latter procedure a marketing licence in one of the Member States (except Portugal) is required before application in other Member States. The Multi-State and "High Tech" (other products: Category B.) procedures are optional. When the procedures are started, all Member States concerned are involved in evaluation of full or abbreviated dossiers through mediation of the European Commission represented by the CPMP (Committee for Proprietary Medicinal Products), Brussels, Belgium. No application for a marketing licence of Category A. products is allowed without mediation of the CPMP. For Category B. products the applicant may opt for a national submission in one or more of the Member States without using the "High Tech" procedure. However, after consultation with the competent authority in one of the Member States, a "High Tech" procedure for Category B. products might still be advisable, but the applicant is not required to follow this procedure. Both the "High Tech" and the Multi-State procedure are currently executed by the mediation of a rapporteur, who liaises with the applicant from the start of the "High Tech" procedure. Ideally, the applicant should contact a licencing authority some 6 to 9 months before an application is planned: to ensure that the near future submission is acceptable. The institution of a rapporteur (appointed by the licencing authority in the country from where the procedure has recently been established) is introduced for the Multi-State procedure.(ABSTRACT TRUNCATED AT 400 WORDS)

Biotechnology↗
PubMed1990

Biochemistry and biotechnology of amino acid dehydrogenases.

Over the last decade, amino acid dehydrogenases such as alanine dehydrogenase (Ala DH), leucine dehydrogenase (Leu DH), and phenylalanine dehydrogenase (Phe DH) have been applied to the enantiomer-specific synthesis and analysis of various amino acids. In perticular, amino acid dehydrogenases from thermophiles have received much attention because of their high stability. Their productivity was enhanced and the purification facilitated by the gene cloning. The advances in biotechnological applications of these enzymes are based on fundamental studies concerning characteristics of the enzymes and reaction mechanism as described in this chapter. Further elucidation of the structure and function of these enzymes based on genetic engineering and protein engineering may enable their properties to be improved for their future uses in biotechnology.

Amino Acid Oxidoreductases↗
PubMed1997

Forest tree biotechnology.

The forest products industry has traditionally viewed trees as merely a raw, and more or less immutable, natural resource. However, unlike such inanimate resources as metallic ores, trees have the potential to be modified genetically, essentially transmuting lead into gold. Increasingly, modern alchemists are applying the tools of biotechnology in efforts to reduce the biological constraints on forest productivity. Several new methodologies being used to address problems in forest biology are described with respect to their potential impact on forest tree improvement. In addition to addressing problems inherent to the current use of trees for production of pulp and paper or solid wood products, genetic manipulation of trees brings with it the potential to create new industries based on the novel characteristics of transgenic trees, e.g. trees containing transgenes to detoxify specific pollutants could be used in the remediation of sites contaminated with hazardous wastes. Efforts to modify trees through biotechnology are in their infancy, and this review seeks to outline the underpinnings of what will undoubtedly be an area of increased emphasis in the next millennium.

Biotechnology↗
PubMed1996

Chromatography in the downstream processing of biotechnological products.

Chromatography techniques are essential for the isolation and purification of most of the high value products of modern biotechnology. The economically sensible and technically satisfactory downstream processing of a therapeutic protein, usually involves a number of chromatographic steps. Its development and optimization require considerable knowledge of the various physico-chemical and engineering aspects of biochemical chromatography. This review addresses the various modes of chromatography and the design of chromatographic separation processes from a biotechnologist's point of view. Strategies for optimizing the structure of the downstream process are outlined and scaling up consideration are discussed. The importance of the different chromatographic methods in research and development is estimated in an analysis of protein purification schemes recently published in the literature. Finally, examples of the application of chromatographic procedures for process scale product purification in the biotechnological industry are given.

Biotechnology↗