Molecular Biotechnology: Principles and Applications - Glick B., Pasternak J. 2002

Fundamentals of Molecular Biotechnology
The Molecular Biotechnology Revolution
The Emergence of Molecular Biotechnology

In the early 1970s, traditional biotechnology was not widely recognized as a scientific discipline; research in this field was primarily conducted within chemical engineering departments and occasionally under applied microbiology programs. In a broad sense, biotechnology is concerned with The production of commercial products generated by microorganisms As a result of their life processes. More formally, biotechnology can be defined as the "application of scientific and engineering principles to the Processing of Materials by biological agents to provide goods and services." Historically, biotechnology originated when Yeast was first used in brewing and Bacteria were employed to make yogurt. The term "biotechnology" was coined in 1917 by Hungarian engineer Karl Ereky to describe the large-scale rearing of pigs using sugar beets as feed. According to Ereky's definition, biotechnology is "all lines of work by which products are produced from raw materials with the aid of living organisms." However, this highly accurate definition did not gain immediate widespread acceptance. For a long time, the term "biotechnology" referred to two very different disciplines. On the one hand, it was used in reference to industrial Fermentation, and on the other, to the field now known as ergonomics. This ambiguity ended in 1961 when Swedish microbiologist Carl-Göran Hedén recommended changing the name of the scientific journal "Journal of Microbiological and Biochemical Engineering and Technology", which specialized in publishing papers on applied microbiology and industrial fermentation, to "Biotechnology and Bioengineering". From that moment on, biotechnology became clearly and irreversibly associated with research into the "industrial production of goods and services with the aid of living organisms, biological systems, and processes," establishing itself on the solid foundation of microbiology, biochemistry, and chemical engineering.

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Fig. 1.1. Key stages of a biotechnological process. The term was introduced by Karl Ereky and referred to the large-scale production of pork (final product) using cheap sugar beets (raw material) as pig feed (biotransformation).

An industrial biotechnological process that utilizes microorganisms to manufacture commercial products typically consists of three key stages (Fig. 1.1).

1. Upstream processing: Treatment of raw materials so that they can be used as a nutrient source for the target microorganism.

2. Fermentation and biotransformation: growth of the target microorganism in a large (typically >100 L) bioreactor (fermentation), followed by the production of the desired metabolite, such as an antibiotic, amino acid, or protein (biotransformation).

3. Downstream Processing: purification of the desired substance from the culture medium components or Cell mass.

The goal of biotechnological research is to maximize the efficiency of each of these stages and to discover microorganisms capable of producing the desired substances (food additives, Antibiotics, etc.). In the 1960s and 1970s, this research focused almost exclusively on upstream processing, bioreactor design, and downstream processing. This led to improved instrumental control of the fermentation process and significantly expanded the capabilities of large-scale cultivation, thereby increasing the production efficiency of several products.

The biotransformation stage was the most difficult to optimize. When wild-type microbial strains were used, the yield of the final product was often far below optimal. Consequently, attempts were made to alter the genetic makeup of existing production strains using chemical mutagenesis or ultraviolet irradiation. With this approach, the level of increased production was typically limited by purely biological factors. For instance, if a mutant strain synthesized too much of a particular substance, this often adversely affected other metabolic processes, leading to growth inhibition during large-scale cultivation. Nevertheless, traditional strategies of "induced mutagenesis and Selection" aimed at strain improvement were exceptionally fruitful for many processes, such as antibiotic production.

Traditional schemes for the genetic improvement of bacteria involve screening, selecting, and testing a vast number of colonies, making such approaches highly expensive and time-consuming. Furthermore, they can only enhance pre-existing, heritable traits of a strain rather than expand its genetic capabilities. Nevertheless, by the late 1970s, the manufacturing processes for a wide range of products had been improved in this manner.

With The Development of Recombinant DNA technology, The Nature of biotechnology changed completely and irreversibly. It became possible to optimize the biotransformation stage in a more direct way, to design rather than merely select high-yielding strains, and to use microorganisms and Eukaryotic Cells as "biological factories" for the PRODUCTION OF Insulin, interferon, Growth Hormone, viral Antigens, and a multitude of other Proteins. Recombinant DNA technology enables the large-scale production of valuable low-molecular-weight substances and macromolecules that are synthesized in only minute amounts under natural conditions. Plants and animals have become natural bioreactors, producing novel or modified Gene products that could never have been created through mutagenesis and selection or crossbreeding. Finally, this new technology facilitates the development of fundamentally new Methods for diagnosing and treating various diseases. At the intersection of recombinant DNA technology and biotechnology, a dynamic and highly competitive new field of research has emerged—molecular biotechnology. This young discipline, much like molecular biology during its formative years, is highly ambitious, and its claims do not always match its real-world capabilities. Its strategy and experimental framework are undergoing rapid changes, with some approaches constantly being superseded by others. Yet one thing is certain: in the future, molecular biotechnology will become a routine method for engineering living systems with novel Functions and capabilities.

Table 1.1. METABOLISM/13.html">History of the development of molecular biotechnology

Fig. 1.2. Molecular biotechnology integrates achievements from many scientific fields, enabling the creation of a wide range of commercial products and methods.

New scientific disciplines rarely emerge in a vacuum; as a rule, they are built upon foundations laid by various other fields of science. In the case of molecular biotechnology, its biotechnological component is rooted in industrial microbiology and chemical engineering, while its molecular component stems from molecular biology, bacterial Molecular Genetics, and nucleic acid enzymology (Table 1.1). Broadly speaking, molecular biotechnology draws upon achievements from a wide array of scientific disciplines and applies them to create a diverse range of commercial products (Fig. 1.2).