ISSN 10227954, Russian Journal of Genetics, 2015, Vol. 51, No. 4, pp. 365–376. © Pleiades Publishing, Inc., 2015.
Original Russian Text © V.G. Debabov, 2015, published in Genetika, 2015, Vol. 51, No. 4, pp. 443–455.
The microbiological industry (the production of
valuable substances by a method of microbiological
synthesis) is today a part of rapidly developed biotech
nology. The growth rates of this industry outstrip aver
age growth rates in other sectors, which is determined
both by the growth of the production of traditional
products (such as amino acids, enzymes) and by the
development of new areas (biofuel, chemicals, biode
gradable plastics) (table).
The parameters of the microorganism producer strain
crucially determine the process economics and the possi
bility of its industrial realization itself. Producer strains
are now frequently called microbial cell factories (MCF).
The traditional requirements for an industrial strain are
its safety, stability, high product yield per substrate unit
(g product per g substrate), high biosynthesis rate
(g product/L/hour), high final concentration (g/L), and
the absence of admixtures that are hard to separate.
Modern strains have impressive characteristics.
Thus, the producer of Lthreonine on the basis of
has a conversion approximately 53% (g amino
acid per g glucose), a biosynthesis rate of approxi
mately 4.2 g/L/h, and a final concentration of approx
imately 150 g/L. The indicators of Llysine producer
on the basis of the
have even higher
If the production of traditional products (such as
amino acids, enzymes, antibiotics) is possible for such
raw material as saccharose and glucose obtained from
starch hydrolyzates (that is, on alimentary raw mate
rial), the future production of biofuel and chemicals
(which should by measured by tens and hundreds of
millions tons by 2020) requires a transition to another
(not alimentary) raw material. Lignocellulose (that is,
wood, straw and other agricultural waste products) will
be such a raw material in the near future. The creation
of strains that are able to efficiently assimilate ligno
cellulose hydrolyzate sugars is a topical problem for
researchers today. Gasification with the receipt of syn
thesis gas (that is, mixture of CO,
) is the
most universal means of lignocellulose processing.
Microorganisms can, in principle, use the synthesis
gas as a single source of carbon and energy [1, 2]. The
creation of producers that use this raw material is an
important challenge for modern science.
It is possible that the mastering of electrobiosyn
thesis using electrogenic microorganisms (which are
able to create biosynthesis based on
current ) will become important in the more remote
future. A problem that is due to the development of the
industry of biofuel and chemicals arises: organization
of the biosynthesis of substances that were not previ
ously synthesized by microorganisms (that is, the
problem of organization of new biochemical pathways
in microbial cell).
Modern Approaches to the Creation
of Industrial Microorganism Strains
V. G. Debabov
State Research Institute of Genetics and Selection of Industrial Microorganisms, Moscow, 117545 Russia
Received October 13, 2014
—Microorganism producer strains are the basis of industrial biotechnology. Their properties deter
mine the economical parameters of the production. Methods of rational design (metabolic engineering) and
combinatorial methods of mutagenesis and selection (laboratory evolution, adaptive evolution, protein and
genomic shuffling) are used for the construction of microorganism strains. Combination of these methods is
frequently used. Modern strains usually do not contain plasmids and markers of drug resistance. All changes
are introduced into the chromosome by the methods of homologous and sitespecific recombination. The
sum of such approaches is called recombineering. Gene expression is carried out at the optimal level under
the control of promoters of a certain power (frequently regulated). Knowledge of a complete genomic
sequence is almost a mandatory condition for the use of methods of metabolic engineering. Bioinformatics
significantly assists in the selection of enzymes and the search for necessary genes and metabolic reactions.
Measurement of metabolic fluxes largely assists in the construction of strains. The current level of science
makes it possible to construct metabolic pathways
in strains for the production of chemicals and bio
fuel. Carbon dioxide has potential as a raw material for microbiological industry; therefore, the study of CO
fixation by acetogens and electrogens is a promising direction of studies.