While fermentation has been important since prehistoric times, it really took off at the beginning of the 20th century when microorganisms were used to make organic acids.
By the 1940s, antibiotic production had become the new application and this moved microbes to the forefront of industrial biology. From the 1940s to the 1970s, the discovery of new antibiotics continued to contribute to the importance of microbial fermentations. Also at this time, production of primary metabolites such as amino acids, organic acids, and vitamins pushed the fermentation field into the spotlight.
Production was dependent on making mutants that produced higher titers of products, but this was difficult, time-consuming, and slow. Thanks to the discovery of recombinant DNA and the establishment of the biotechnology industry in California in 1971–1973, entirely new ways of improving microorganisms became available and it revolutionized the fermentation industry.
Microbes are one of the greatest sources of metabolic and enzymatic diversity. Emerging recombinant DNA and genomic techniques have led to efficient new expression systems, modification of biosynthetic pathways leading to new metabolites by metabolic engineering, and enhancement of catalytic properties of enzymes by directed evolution.
Complete sequencing of industrially important microbial genomes is taking place very rapidly and there are already dozens of genomes sequenced. Functional genomics and proteomics are indeed major tools used in the search for new molecules and development of higher-producing strains.
Advantages of Microbes
Natural products are superior to synthetic compounds for making pharmaceuticals. Microbes are better than plants or animals for manufacturing commercial levels of such compounds.
Microbes have a number of advantages, including rapid uptake of nutrients supporting high rates of metabolism and biosynthesis; ability to carry out a wide variety of reactions; facility to adapt to a large array of different environments; ease of genetic manipulation, both in vivo and in vitro, to increase production, to modify structures and activities, and to make entirely new products; simple screening procedures; and a wide diversity.
Microbial products are diverse, ranging from large molecules such as proteins, nucleic acids, carbohydrate polymers, or even cells, to small molecules that are usually divided into primary metabolites, i.e., those essential for vegetative growth, and secondary metabolites, which are not essential for growth. The primary metabolites include amino acids, organic acids, alcohols, and vitamins.
Production of a particular primary metabolite by deregulated organisms may inevitably be limited by the inherent capacity of the particular organism to make the appropriate biosynthetic enzymes. Recent approaches utilize modern genetic engineering techniques to correct such deficiencies and develop strains overproducing primary metabolites.
There are two ways to accomplish this: increase the number of copies of structural genes coding for these enzymes and the frequency of transcription.
Novel genetic technologies are important for the development of overproducers. Genome-based strain reconstruction leads to the development of a superior strain which contains mutations crucial to hyperproduction but not other unknown mutations, which accumulate by brute-force mutagenesis and screening.
Also important are genome-sequencing projects involving hundreds of genomes, the availability of sequences corresponding to model organisms, new DNA microarray and proteomic tools, and new techniques for mutagenesis and recombination DNA technology.