Modifications done to intermediate metabolism with use of recombinant DNA techniques is metabolic engineering. Related terminologies include molecular evolution, metagenomics, and proteomics. Genetic material cloning from microorganisms, which cannot be lab- grown, to identify new forms of genes is metagenomics. The identification of expressed gene functional proteins using mass spectroscopy (MS) techniques is proteomics. The variation of selected protein amino acids at a genetic level is molecular evolution. Proteins with altered characteristics or functions are expressed by these modified genes.

Classical microbial screening aims to achieve:
(1) modified cell properties;
(2) improve protein or molecule production made by a microorganism;
(3) adding new catabolic activities for toxic chemicals that degrade;
(4) substrate range extension; and
(5) adding metabolic pathways to enable the host to produce new chemicals.

Metabolic Engineering- A Study

Metabolic engineering has developed to evolutionary heights. Development and breeding of animals and plants has been under research for centuries. Microorganisms have been selected and improved for more than 100 years now. The manner followed by microorganisms in utilizing substrates of carbon for energy and for carrying out biosynthesis, based on metabolic pathways assessment, and metabolic pathway changes, via externally applied screening and mutagenesis methods, has been underway for more than 50 years. The alterations done to an organism's genetic setup in terms of adding, changing, and deleting the characteristic features of a specific gene is quite recent.

Since 1973, molecular biology has seen a huge expansion in methods by which microorganisms' productivity can be enhanced for biotherapeutic proteins expression and industrial manufacture of commercially valuable products. Molecular evolution, also known as direct evolution, describes the evolutionary principles of an organism's new or improved traits. These principles have been used by microbiologists for the past 100 years, while humans started using these principles since the domestication of animals and plants more than 8000 years ago.

Evolutionary Principles

In biotechnological context, this process has been described as applied microbiology and biochemical engineering. The importance of evolutionary principles is based on the variability of the selected traits of organisms. Since variability is based on genetics, traits can be passed on to an offspring of an organism. Selection better favors organisms, which are have the ability to compete for limited resources in an environment. This leaves more space for off-spring to compete. Over generations and time, organisms and the descendants that are able to compete the best will dominate. From the perceptive of metabolic engineering, there are certain ways to direct an organism's evolution: the environment (selective pressure) and genetic variability.

Before 1976, in microbiology, an organism's evolution was accomplished by altering the growing conditions (environment) by controlling pH, media composition, temperature, and other parameters that favor the microorganism selection using desirable traits that grow quickly under altered conditions. Genetic variability arises from either natural genome variations in a microorganism or from genetic sequences alterations due to random or spontaneous mutations or human induced random mutations via the applications of radiation or mutagenic chemicals to the microorganisms.

Neutral Mutation

Few mutations, called as neutral mutation, do not affect an organism's fitness. Some mutation renders an organism less fit thus reducing the organism's ability to compete.

Only a very few makes the organism more fit thereby enabling the organism to compete better. The selection power depends on the result that deleterious and neutral mutations are eliminated and beneficial mutations survive. Through continually repeating generations, affected by selection, traits are designed through iterative trial and error.

Since the evolution of molecular biology in 1976, tools have achieved success in removing randomness to a great deal and have also reduced number of selective culturing that is required to produce an organism with the desired traits. Additionally, since genes from different organisms can be inserted into a target organism has allowed the development of mammalian cells or microorganisms that produce erythropoietin (EPO) (hormone that promotes the red blood cell production) and insulin (tPA) (plasminogen activator). These molecules are next to impossible to generate using random mutations. Medical products that are associated with biotechnology have brought in improvements in microorganisms thereby improving their productivity in producing existing products such as lactic acid, enzymes, and ethanol to name a few.

Advances in metabolic engineering have improved human ability to control and select the propagation of desired traits.

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