Effect of the genistein metabolite on leptin secretion in murine adipocytes in vitro

► 2-(4-Hydroxyphenyl)propionic acid (2-HPPA) enantiomers were separated by HPLC. ► We prepared an optically active 2-HPPA from genistein by strain SY8519. ► (S)-2-HPPA was synthesized from (S)-2-phenylpropionic acid. ► We determined the stereochemistry of SY8519-producing 2-HPPA as an R-configuration. ► Genistein attenuates the leptin-reducing activity by the metabolism to (R)-2-HPPA. Soy isoflavonoids have many useful properties. However, they are metabolized in vivo, including in humans. The effect of the metabolism of soy isoflavonoids on their properties is not fully understood. We have isolated the bacterial strain SY8519, which has been shown to metabolize daidzein to O-desmethylangolensin and to produce 2-(4-hydroxyphenyl)propionic acid from genistein. According to chiral HPLC analysis, the 2-(4-hydroxyphenyl)propionic acid obtained from the bacterium was optically active. To determine the absolute stereochemistry of the microbial product, we prepared (S)-2-(4-hydroxyphenyl)propionic acid from (S)-2-phenylpropionic and concluded that the microbial product had an R-configuration by chiral HPLC analysis. We also applied the metabolite to mouse adipocytes and found that 2-HPPA was less effective at reducing leptin secretion than the parent compound genistein. Our results suggested that ‘O-desmethylangolensin-production’ attenuates the effect of soy isoflavonoids by reducing not only the activity of daidzein but also that of genistein.