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Biotechnological production of pyruvic acid.

Pyruvic acid is an important organic acid widely used in the chemical and drug, as well as agrochemical, industries. Compared with the chemical method, biotechnological production of pyruvic acid is an alternative approach because of the low cost. An overview of biotechnological production of pyruvate, including direct fermentative production employing eukaryotic and prokaryotic microorganisms, production by a resting cell method and an enzymatic method as well as the recovery of pyruvate, is discussed. A multi-vitamin auxotrophic yeast strain, Torulopsis glabrata. has been used in the commercial production of pyruvate; emphasis is therefore placed on the mechanism and characteristics of pyruvate production by this strain.

Biotechnology↗

Thermozymes: biotechnology and structure-function relationships.

Recent findings on the biochemical and molecular features of the following thermozymes are presented, based on their biotechnological use: alpha-amylase and amylopullulanase, used in starch processing; glucose isomerase, used in sweetener production; alcohol dehydrogenase, used in chemical synthesis; and alkaline phosphatase, used in diagnostics. The corresponding genes and recombinant proteins have been characterized in terms of sequence similarities, specific activities, thermophilicity, and unfolding kinetics. Site-directed and nested deletion mutagenesis were used to understand structure-function relationships. All these thermozymes display higher stability and activity than their counterparts currently used in the biotechnology industry.

Alcohol Dehydrogenase↗

Alpha-L-arabinofuranosidases: the potential applications in biotechnology.

Recently, alpha-L-arabinofuranosidases (EC3.2.1.55) have received increased attention primarily due to their role in the degradation of lignocelluloses as well as their positive effect on the activity of other enzymes acting on lignocelluloses. As a result, these enzymes are used in many biotechnological applications including wine industry, clarification of fruit juices, digestion enhancement of animal feedstuffs and as a natural improver for bread. Moreover, these enzymes could be used to improve existing technologies and to develop new technologies. The production, mechanisms of action, classification, synergistic role, biochemical properties, substrate specificities, molecular biology and biotechnological applications of these enzymes have been reviewed in this article.

Biotechnology↗

Measuring biotechnology employees' ethical attitudes towards a controversial transgenic cattle project: the ethical valance matrix.

What is the relationship between biotechnology employees' beliefs about the moral outcomes of a controversial transgenic research project and their attitudes of acceptance towards the project? To answer this question, employees (n=466) of a New Zealand company, AgResearch Ltd., were surveyed regarding a project to create transgenic cattle containing a synthetic copy of the human myelin basic protein gene (hMBP). Although diversity existed amongst employees' attitudes of acceptance, they were generally: in favor of the project, believed that it should be allowed to proceed to completion, and that it is acceptable to use transgenic cattle to produce medicines for humans. These three items were aggregated to form a project acceptance score. Scales were developed to measure respondents' beliefs about the moral outcomes of the project for identified stakeholders in terms of the four principles of common morality (benefit, non-harm, justice, and autonomy). These data were statistically aggregated into an Ethical Valence Matrix fo the project. The respondents' project Ethical Valence Scores correlated significantly with their project acceptance scores (r=0.64, p<0.001), accounting for 41% of the variance in respondents' acceptance attitudes. Of the four principles, non-harm had the strongest correlation with attitude to the project (r=0.59), followed by benefit and justice (both r=0.54), then autonomy (r=0.44). These results indicate that beliefs about the moral outcomes of a research project, in terms of the four principles approach, are strongly related to, and may be significant determinants of, attitudes to the research project. This suggests that, for employees of a biotechnology organization, ethical reasoning could be a central mechanism for the evaluation of the acceptability of a project. We propose that the Ethical Valence Matrix may be used as a tool to measure ethical attitudes towards controversial issues, providing a metric for comparison of perceived ethical consequences for multiple stakeholder groups and for the evaluation and comparison of the ethical consequences of competing alternative issues or projects. The tool could be used to measure both public and special interest groups' ethical attitudes and results used for the development of socially responsible policy or by science organizations as a democratizing decision aid to selection amongst projects competing for scarce research funds.

Agriculture↗

The debate over food biotechnology in the United States: is a societal consensus achievable?

Unless the public comes to agree that the benefits of food biotechnology are desirable and the associated risks are acceptable, our society may fail to realize much of the potential benefits. Three historical cases of major technological innovations whose benefits and risks were the subject of heated public controversy are examined, in search of lessons that may suggest a path toward consensus in the biotechnology debate. In each of the cases--water fluoridation, nuclear power and pesticides--proponents of the technology gathered scientific evidence that they believed established that the innovations were safe. In each case, the federal government was heavily involved in oversight, safety regulation, and in the first two cases, active promotion of the technology. Supporters of the technologies employed a variety of communications strategies, ranging from massive "educational" campaigns (e.g. "Our Friend The Atom") to vituperative ad hominem attacks on leading opponents. None of these strategies succeeded in achieving broad societal acceptance of the technologies. Fluoridation today is opposed as vigorously by activist groups as it was when first introduced around 1950; it has not been universally adopted even in the U.S., and it has been rejected in most other countries. The American nuclear power industry is moribund, and the public has essentially rejected the technology. The pesticide industry is thriving, with new generations of products succeeding older more hazardous chemicals in a constant cycle. However, strong regulation has failed to prevent adverse health and ecological effects, which have been empirically associated with pesticide uses after the chemicals were dispersed in the environment. Debate over whether risks of such effects are acceptable has been heated for four decades, with scientists and the public divided.

Biotechnology↗

Ethics and patentability in biotechnology.

The systems of patent rights in force in Europe today, both at the level of national law and on the regional level, contain general clauses prohibiting the patenting of inventions whose publication and exploitation would be contrary to "ordre public" or morality. Recent years have brought frequent discussion about limiting the possibility of patent protection for biotechnological inventions for ethical reasons. This is undoubtedly a result of the dynamic development in this field in the last several years. Human genome sequencing, the first successful cloning of mammals, and the progress in human stem cell research present humanity with many new questions of an ethical nature. Directive 98/44 of the European Parliament and of the Council of July 6, 1998, on the Legal Protection of Biotechnological Inventions created a new basis for patent protection in this field of technology. Based on the European experience to now, however, it must be said that patent law is not the right place to legislate the consequences of the morality of an invention.

Bioethics↗

Review: methods of monitoring for process micro-organisms in biotechnology.

Biotechnology encompasses the use of micro-organisms and other biological agents in a range of processes, including the production of pharmaceuticals, fine chemicals, enzymes, food and drink. This review looks at the sources of occupational exposure by describing the way in which process micro-organisms, some of which could be hazardous to health, can be released into the workplace or the environment. It also examines current practices, monitoring strategies and procedures used to monitor for release of micro-organisms during biotechnology processes and looks forward to methods that may be of use in the future.

Air Microbiology↗

Development of biotechnology control systems.

Advances in genetic engineering have generated great interest in biotechnology systems. Modern fermentation processes have a more scientific basis and can be optimized more quickly by utilizing instrumentation and control technology that permits increasing yield and product quality. The automation technology, to a large extent, can determine the degree of success of growing microorganisms. The automation system in modern biotechnology facilities includes a number of leading technologies such as sensors, indicators, data acquisition, distributed control, programmable control, communications, data base management, on-line data analysis techniques and application software. Modern computer systems have made fermentation processes easier and more accurate by performing tasks such as on-line analysis, statistical process control and supervisory control, while microprocessor-based distributed process controllers perform direct digital control, batch and sequencing control. This paper addresses technical issues related to the development of instrumentation and control systems that integrate these technologies through methodologies that permit the timely generation of the documentation and drawings that specify the control system for procurement, installation, commissioning, validation and operation.

Biotechnology↗

Application of ultrasound to biotechnology: an overview.

Application of ultrasound to biotechnology is relatively new, but several processes that take place in the presence of cells or enzymes are activated by ultrasonic waves. High intensity ultrasonic waves break the cells and denaturize the enzymes. Low intensity ultrasonic waves can modify cellular metabolism or improve the mass transfer of reagents and products through the boundary layer or through the cellular wall and membrane. In the case of enzymes, the increase in the mass transfer rate of the reagents to the active site seems to be the most important factor. Immobilized enzymes are more resistant to thermal deactivation produced by ultrasound than native enzymes. Reverse micelles can be used to carry out synthesis using enzymes. Several applications of ultrasound to the biotechnology are discussed.

Biotechnology↗

Biotechnology and its public.

The author provides a perspective on three key areas of biotechnology: the public debate over hazards, the commercialization of the technology, and ethical issues that are arising in terms of application of genetic therapy to humans. He reviews the history of the recombinant DNA research debate beginning at Asilomar in 1975, when the molecular biologists called for a temporary moratorium on certain experiments, so the NIH might develop guidelines to govern this research. The author then characterizes the lobbying activities of the biologists against proposed regulation at the federal, state and local level. Despite the lobbying, he concludes that Congress did not enact legislation because of the exemplary behavior of the biologists, beginning with their meeting at Asilomar. The author next describes the impact commercialization of this technology will have on academic biologists who traditionally have not been involved in that process (as have chemists and physicists). He also comments on the ethics of biotechnology, concluding that the more powerful biology becomes, the more its uses and some control of those uses will be debated.

Biotechnology↗

Biotechnology of the Archaea.

The Archaea, designated since 1979 as a separate Super-Kingdom (the highest taxonomic order), are a highly novel group of microorganisms which look much like bacteria but have many molecular and genetic characteristics that are more typical of eukaryotes. These unusual organisms can be conveniently divided according to their 'extreme' environmental niche, into three broad phenotypes: the thermophiles, methanogens and extreme halophiles. Each group has unique biochemical features which can be exploited for use in the biotechnological industries. The extreme molecular stability of thermophile enzymes, the novel C1 pathways of the methanogens and the synthesis of organic polymers by some halophiles are all currently or potentially valuable examples of the biotechnology of the Archaea.

Archaea↗

A perspective on the biotechnological potential of extremophiles.

It is well recognized that many environments considered by man to be extreme are colonized by microorganisms which are specifically adapted to these ecological niches. A diverse range of bacteria, cyanobacteria, algae and yeasts have been isolated from such habitats and it is now widely accepted that these microorganisms provide a valuable resource not only for exploitation in novel biotechnological processes but also as models for investigating how biomolecules are stabilized when subjected to extreme conditions. This short review summarizes our current state of knowledge of this unique group of microorganisms and their enzymes, and attempts to identify their future biotechnological potential.

Bacteria↗

Patent information in biotechnology.

Patents represent an important source of scientific and legal information. Unfortunately, many of the major sources of biotechnology scientific information (for example, Medline and Biosis) do not index patents. It is probable that information of importance to the field of biotechnology reported in patents is not available in the scientific-journal literature. This article gives a brief overview of patent law from the standpoint of the technical information content of patents, and provides a survey of relevant sources of patent information for retrospective searching and for current awareness.

Biotechnology↗

Environmental carcinogenesis and biotechnology.

Numerous environmental and host factors, some of which are known and some unknown, contribute to cancer development. While data and studies abound, our current understanding of the relation between cancer and the environment is still very limited. Understanding environmental carcinogenesis is critical to its effective management. Biotechnology has revolutionalized the study of biological and biomedical sciences. This minireview provides an overview of environmental carcinogenesis with emphasis on the contributions and prospects of biotechnology in advancing an understanding of environmental carcinogenesis for its prevention and intervention.

Animals↗

Immuno- and flow cytometric analytical methods for biotechnological research and process monitoring.

In this article, the applications of immunoanalysis and flow cytometry for research and process monitoring in biotechnology are discussed. Brief reviews of the two analytical methods are followed by descriptions of actual applications in various areas of biotechnology. In the case of immunoanalysis, emphasis is placed on systems for on-line bioprocess monitoring, and examples are given for a thermostable pullulanase, a mouse IgG, and antithrombin III. Although flow cytometry is not currently an on-line analytical technique, its value as an off-line method is illustrated by examples of the measurement of shear stress effects, lipid content, and sterol content.

Animals↗

Food, agricultural and marine biotechnology in Chile.

Economic segments with highest growth rates in Chile are those based on renewable resources like agriculture (fruits and vegetables), marine and forest products. Opportunities for biotechnology are based on a sound scientific base at universities, adequate funding and incipient industry-academia relationships. However, there is an urgent need to develop the engineering capabilities required to scale-up processes and to design, build and operate industrial biotechnology plants.

Agriculture↗

Difficulties in conceiving and applying guidelines for the safety evaluation of biotechnologically-produced drugs: some examples.

Pharmaceutical companies and regulatory authorities need guidelines for the safety evaluation of all drugs. Nevertheless, new types of drugs, e.g. biological products produced by novel biotechnological processes (as recombinant DNA methods), induce new problems for this evaluation. The following points will be assessed: (1) As a postulate, safety is highly dependent on the industrial process and on the controls. (2) To conceive guidelines, it is necessary to take into account the structure of the pharmaceutical product compared with the natural biological product (identical or not), the therapeutical use and the relevance of the classical toxicological investigations: for example single dose toxicity gives poor results for target organs, repeated dose toxicity is related to immunogenicity, mutagenicity testing is debatable. (3) To apply guidelines is still more difficult, for example to select animal models (animal models of diseases), define dose levels, evaluate immunogenicity, conceive the design of reproduction studies and the feasibility of cancerogenicity studies. Therefore, common sense and a case-by-case approach are necessary (guidance vs. guidelines) for the safety evaluation of drugs produced by biotechnology, and an early collaboration between all the partners (companies, experts and regulatory authorities).

Animals↗

Validation of biotechnology products and processes.

Recent advances in the validation of biotechnology products have focused on clearer definitions of the requirements for cleaning validation, especially for multi-product facilities. In addition, sensitive analytical methods have been developed that can be validated. This, together with computer validation, has contributed to the biotechnology industry's ability to demonstrate the production of safe and efficacious products for biotherapeutic and diagnostic purposes.

Animals↗