Computational analysis of SULT1A1 allozymes reveals potential mechanisms of inter-individual variability in (poly)phenol metabolism

Inter-individual variability in (poly)phenol metabolism can significantly influence health effects, yet its mechanisms are poorly understood. Through a validated multi-tiered computational workflow, this study explored how a single nucleotide polymorphism (SNP) in the SULT1A1 gene (SULT1A1-F247L, forming SULT1A1*5 allozyme) might influence the sulfation of 20 dietary (poly)phenols. The methodological approach combined molecular docking and molecular dynamics simulations, monitoring hydroxy group orientation toward the PAPS cofactor sulfate – an essential requirement for efficient sulfation. Among the (poly)phenols examined, several compounds were stably recruited by both allozymes, suggesting limited polymorphism effects on their sulfation. Conversely, SNP-specific sulfation preferences were recorded for daidzein, isourolithin A, and various γ-valerolactone derivatives. This study shows how SNPs may selectively influence metabolic fates of specific (poly)phenols regardless of chemical subclasses, providing a valuable proof-of-principle addressing the variability of their metabolism among humans. This methodology provides a basis for understanding the mechanisms underlying inter-individual variability, explaining individual responses to (poly)phenol-rich foods.