麻豆淫院

A novel evolutionary technique, designed to select E. coli strains capable of more efficiently metabolizing acetate鈥攁 sustainable, cost-effective carbon source鈥攈as been developed by a research team led by Professor Donghyuk Kim from the School of Energy and Chemical Engineering at UNIST, in collaboration with Professor Gyoo Yeol Jung from POSTECH and Dr. Myung Hyun Noh from the Korea Research Institute of Chemical Technology (KRICT).

Strains evolved through this method demonstrate a 1.7-fold increase in their ability to convert acetate into itaconic acid, a key raw material for eco-friendly adhesives and bioplastics. The team anticipates that this advancement paves the way for transforming microbial cell factories into stable, efficient producers of chemical raw materials. This research was in Bioresource Technology.

Itaconic acid is a biodegradable polymer and a key component in medical adhesives. Currently, it is predominantly produced via fermentation of starches by fungi, a process that consumes significant food resources and incurs high production costs.

As an alternative, acetate鈥攎ainly derived from vinegar鈥攐ffers a cheap and abundant substrate. Moreover, utilizing acetate coupled with carbon dioxide capture can contribute to carbon reduction efforts. However, microbes typically struggle to efficiently metabolize acetate due to toxicity and metabolic burden, resulting in limited itaconic acid yields.

To overcome this challenge, the research team employed an adaptive laboratory evolution (ALE) approach, selecting for strains that thrive on high itaconic acid levels. They integrated biosensors鈥攄esigned to express antibiotic resistance genes in response to acetate-derived itaconic acid concentrations鈥攊nto E. coli. By gradually increasing antibiotic levels during repeated cultivation cycles, only those strains capable of producing high levels of itaconic acid survived and thrived.

After approximately 50 generations of laboratory evolution, the team isolated strains exhibiting 1.7 times higher itaconic acid production and faster cell division rates compared to the original strains.

To elucidate the genetic basis of these improvements, whole-genome and transcriptome analyses were performed. Remarkably, the evolved strains possessed a large genomic deletion spanning approximately 31,000 base pairs, including two genes involved in acetate metabolism and growth efficiency. The deletion was found to induce the stringent response, a stress adaptation mechanism, altering cellular physiology to favor enhanced acetate utilization and growth.

Jihoon Woo, the first author of the study, explained, "While the stringent response is typically known to suppress growth and conserve resources under stress, in this case, it surprisingly facilitated the more efficient metabolism of acetate and improved both growth and production."

Further experiments demonstrated that overexpressing relA, a gene responsible for synthesizing the signaling molecule ppGpp that triggers the stringent response, recapitulated the enhanced phenotypes observed in the evolved strains.

Professor Kim commented, "Through this evolutionary and systems biology approach, we reinterpreted microbial physiological responses and turned what was previously considered a disadvantage鈥攖he stringent response鈥攊nto an advantage for bioproduction. This strategy offers promising insights for developing sustainable chemical manufacturing technologies in the post-fossil fuel era."