Science & Technology

Two problems that occur when using bioconversions for commercial purposes are : 1) the utilized micro-organisms are not cultured in their natural environment, and 2) the efficiencies and yields needed are much higher than the ones that naturally occur. As a result further engineering is always needed to reach commercially viable goals.

Classical strain improvement methods have been successful in the past, for example, decades of work has led to impressive increases (up to 10,000 fold) of antibiotic yields in production strains. More recently, using the genomic information and robotic technologies that are available today, several other methods have been developed to improve strains, enzymes and pathways. These generally combine traditional genetic engineering, gene shuffling and a combination of environmental screening for novel genes and aggressive mutagenesis. However, the process of screening individual colonies is still difficult and time-consuming, and inefficiently reproduces the effects of natural selection in a large population of competing individuals. In openly competing populations such as those maintained in the continuous culture apparatii used by Evolugate, the power of Darwinian evolution is used to its full advantage to improve the performance of an enzyme or a pathway.

Indeed, in a continuous culture setting any mutant that has an advantage will overcome the population. Mutations will continually accumulate in the dominant strain, improving its growth rate in the defined environment of the device. At the end of an experiment, the clone dominating the population will be the one that has accumulated the most (and best) adaptive mutations with respect to the targeted phenotypic trait. This technology is complementary to other technology available today, and continuous culture provides a way to more rapidly sort, fix, compare and improve strains that have been mutated by artificial or natural means.

Historically, the value of evolutionary optimization as a process for improving the performance of industrial micro-organisms has been recognized, but industrial use of evolution has been hindered by the difficulty of maintaining large populations of microbial cells under controlled conditions for numerous generations.

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