RESUMEN
With its estrogenic activity, (S)-equol plays an important role in maintaining host health and preventing estrogen-related diseases. Exclusive production occurs through the transformation of soy isoflavones by intestinal bacteria, but the reasons for variations in (S)-equol production among different individuals and species remain unclear. Here, fecal samples from humans, pigs, chickens, mice, and rats were used as research objects. The concentrations of (S)-equol, along with the genetic homology and evolutionary relationships of (S)-equol production-related genes [daidzein reductase (DZNR), daidzein racemase (DDRC), dihydrodaidzein reductase (DHDR), tetrahydrodaidzein reductase (THDR)], were analyzed. Additionally, in vitro functional verification of the newly identified DDRC gene was conducted. It was found that approximately 40% of human samples contained (S)-equol, whereas 100% of samples from other species contained (S)-equol. However, there were significant variations in (S)-equol content among the different species: rats > pigs > chickens > mice > humans. The distributions of the four genes displayed species-specific patterns. High detection rates across various species were exhibited by DHDR, THDR, and DDRC. In contrast, substantial variations in detection rates among different species and individuals were observed with respect to DZNR. It appears that various types of DZNR may be associated with different concentrations of (S)-equol, which potentially correspond to the regulatory role during (S)-equol synthesis. This enhances our understanding of individual variations in (S)-equol production and their connection with functional genes in vitro. Moreover, the newly identified DDRC exhibits higher potential for (S)-equol synthesis compared to the known DDRC, providing valuable resources for advancing in vitro (S)-equol production. IMPORTANCE: (S)-equol ((S)-EQ) plays a crucial role in maintaining human health, along with its known capacity to prevent and treat various diseases, including cardiovascular diseases, metabolic syndromes, osteoporosis, diabetes, brain-related diseases, high blood pressure, hyperlipidemia, obesity, and inflammation. However, factors affecting individual variations in (S)-EQ production and the underlying regulatory mechanisms remain elusive. This study examines the association between functional genes and (S)-EQ production, highlighting a potential correlation between the DZNR gene and (S)-EQ content. Various types of DZNR may be linked to the regulation of (S)-EQ synthesis. Furthermore, the identification of a new DDRC gene offers promising prospects for enhancing in vitro (S)-EQ production.
Asunto(s)
Equol , Isoflavonas , Animales , Humanos , Ratones , Ratas , Porcinos , Equol/genética , Equol/metabolismo , Racemasas y Epimerasas , Pollos/metabolismo , Isoflavonas/metabolismo , Oxidorreductasas/metabolismoRESUMEN
SDR (Short-chain Dehydrogenases/Reductases) are one of the oldest and heterogeneous superfamily of proteins, whose classification is problematic because of the low percent identity, even within families. To get clearer insights into SDR molecular evolution, we explored the splicing site organization of the 75 human SDR genes across their vertebrate and invertebrate orthologs. We found anomalous gene structures in members of the human SDR7C and SDR42E families that provide clues of retrogene properties and independent evolutionary trajectories from a common invertebrate ancestor. The same analyses revealed that the identity value between human and invertebrate non-allelic variants is not necessarily associated with the homologous gene structure. Accordingly, a revision of the SDR nomenclature is proposed by including the human SDR40C1 and SDR7C gene in the same family.