Recombinant bacterium boosts production of compound that can relieve menopause symptoms

Equol is produced naturally in small quantities by the human intestine-abiding bacterium, Slackia isoflavoniconvertens. Clinical studies have shown that this compound reduces hot flashes, night sweats, bone loss, and other menopausal symptoms, with no harmful side effects, and studies in several human cell lines suggest that it might eventually prove to prevent prostate cancer. But the anaerobic S. isoflavoniconvertens' productivity was too low for large-scale production, and that bacterium doesn't work well with industrial fermenters, said lead investigator Byung-Gee Kim, PhD, a professor in the Department of Chemical and Biological Engineering, Seoul National University, Seoul, Korea.

To increase production of (S)-equol, the investigators cloned the enzymes of the compound's biosynthetic pathway into a strain of the laboratory bacterium, Escherichia coli, which is commonly used, among other things, for industrial purposes. But although this bacterium enabled easier control of production, and although the investigators assembled optimum environmental conditions for the bacterium, including its preferred acidity level and temperature, the yield still remained too low for commercial production, said Kim.

The researchers then tried another way to raise production. They identified the rate-determining enzyme in the biosynthetic pathway. "We replaced the slower, naturally-occurring enzyme with a mutant version of that enzyme, which is faster," said Kim.

The mutant enzyme has substantially increased production of (S)-equol. However, the process has yet to achieve sufficient productivity for industrial production, said Kim. "We showed a partial success, and we are working to improve it."