2. Why are microorganisms used in industry?
The importance of the fermentation industry resides in five important characteristics of
microorganisms: (1) a high ratio of surface area to volume, which facilitates the rapid uptake
of nutrients required to support high rates of metabolism and biosynthesis; (2) a tremendous
variety of reactions which microorganisms are capable of carrying out; (3) a facility to adapt
to a large array of different environments, allowing a culture to be transplanted from nature
to the laboratory flask or the factory fermentor, where it is capable of growing on inexpensive
carbon and nitrogen sources and producing valuable compounds; (4) the ease of genetic
manipulation, both in vivo and in vitro, to increase production of the products, to modify
structures and activities, and to make entirely new products; and (5) an ability to make specific
enantiomers, usually the active ones, in cases where normal chemical synthesis yields a
mixture of active and inactive enantiomers.
Microorganisms are important to us for many reasons, but one of the principal ones is that
they produce things of value to us. These may be very large materials such as proteins, nu-A.L. Demain / Biotechnology Advances 18 (2000) 499–514 501
cleic acids, carbohydrate polymers, or even cells, or they can be smaller molecules which we
usually separate into metabolites essential for vegetative growth and those inessential (i.e.
primary and secondary metabolites, respectively). The power of the microbial culture in the
competitive world of commercial synthesis can be appreciated by the fact that even simple
molecules (i.e. L-glutamic acid and L-lysine), are made by fermentation rather than by chemical
synthesis. Although a few products have been temporarily lost to chemical synthesis
(e.g. solvents such as acetone and butanol), it is obvious that most natural products are made
by fermentation technology. Despite the efficiency of the chemical route to riboflavin, much
of the production of this compound is carried out by fermentation; chemical processes to vitamin
C and steroids still employ microbial bioconversion steps. Most natural products are so
complex and contain so many centers of asymmetry that they probably will never be made
commercially by chemical synthesis.
Although microbes are extremely good in presenting us with an amazing array of valuable
products, they usually produce them only in amounts that they need for their own benefit; thus
they tend not to overproduce their metabolites. Regulatory mechanisms have evolved in microorganisms
that enable a strain to avoid excessive production of its metabolites so that it can compete
efficiently with other forms of life and survive in nature. The fermentation microbiologist,
however, desires a ‘wasteful’ strain which will overproduce and excrete a particular compound
that can be isolated and marketed. During the screening stage, the microbiologist is searching for
organisms with weak regulatory mechanisms. Once a desired strain is found, a development program
is begun to improve titers by modification of culture conditions, mutation and recombinant
DNA technology. The microbiologist is actually modifying the regulatory controls remaining in
the original culture so that its ‘inefficiency’ can be further increased and the microorganism will
excrete tremendous amounts of these valuable products into the medium.
The main reason for the use of microorganisms to produce compounds that can otherwise
be isolated from plants and animals or synthesized by chemists is the ease of increasing production
by environmental and genetic manipulation. Thousand-fold increases have been recorded
for small metabolites. Of course, the higher the specific level of production, the simpler
is the job of product isolation.