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Unique growth principles of microorganisms with minimal genome unveiled

About 70% of the world’s antibiotics are made from microorganisms, and are being used in various fields such as chemistry, pharmaceutics, and healthcare. A recent trend is genetic engineering, which involves the manipulation of genomes to produce biofuel and physiologically active compounds. However, genetic engineering has limitations due to the complexity of organisms and genome uncertainty. The minimal genome concept was proposed to reduce the complexity while sustaining life with the bare minimum set of genes, but this resulted in a slow rate of growth. This study restored the growth of minimal genome E. coli and examined the growth principles through comparative analysis with existing microorganisms. The findings are expected to boost the microbial production of valued bioproducts.

Minimal genome relies on smallest set of genes to maintain life

The genome of an organism consists of DNA, which is made up of countless chains of nucleic acids. The team removed non-essential genes to construct a minimal E. coli genome. However, this E. coli grew slowly at about 30% of the normal growth rate. The team mimicked the natural evolutionary process and applied it to the minimal genome E. coli to induce adaptation and evolution in a short period. As a result, the genome was smaller in size but saw an improvement in growth rate (180% of the growth rate of the previous minimal genome). Protein productivity was also significantly enhanced.
According to the team’s multi-omics analysis (covering genome, transcriptome, and translatome), the minimal genome saves energy by eliminating the production of unnecessary genes, and has a reducing power higher by 4.5 times as it uses a different glucose metabolic path compared to regular E. coli. Here, reducing power is what provides the necessary energy to form macromolecules from smaller building blocks within cells. The production of useful compounds such as lycopene (antioxidant) and violacein (antivirus, anticarcinogenic) increased by 80%.

Translational buffering not seen in minimal genome

The constructed minimal genome did not exhibit transitional buffering, which is seen in all microorganisms known to date. Translational buffering refers to how manipulating cells can only produce proteins up to a certain level due to the constraint imposed by cells having limited resources. The minimal genome E. coli, on the other hand, does not experience translational buffering. It is thus capable of producing up to three times the amount of proteins attainable by regular E. coli. This study resolved the slow growth rate of minimal genome through adaptive evolution, and examined the underlying metabolic principles. The high reducing power and low translational buffering demonstrated the advantages of the minimal genome over regular E. coli, such as the higher production of useful compounds and protein production capacity. The results are expected to contribute to the microorganism-based production of useful compounds and biocompounds.

Prof. Cho, Byung-Kwan
2019 KI Annual Report

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