안용진 (서울대학교)

한빛사논문

조회103

서울대학교

Small Methods, Jul 26 2024, | https://doi.org/10.1002/smtd.202400469 Time-Resolved Evaluation of L-Dopa Metabolism in Bacteria-Host Symbiotic System and the Effect on Parkinson's Molecular Pathology

Doyeon Kim ¹, Tin Tin Manh Nguyen ¹, Yechan Moon ¹, Jin-Mo Kim¹, Hoonsik Nam ¹, Dong Seok Cha ², Yong Jin An ¹, Arvie Camille V de Guzman ¹, Sunghyouk Park ¹

¹Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, 08826, South Korea.

²College of Pharmacy Woosuk University, Jeonbuk, 55338, South Korea.

Corresponding Authors: Yong Jin An, Arvie Camille V. de Guzman, Sunghyouk Park

Abstract

The gut microbiome influences drug metabolism and therapeutic efficacy. Still, the lack of a general label-free approach for monitoring bacterial or host metabolic contribution hampers deeper insights. Here, a 2D nuclear magnetic resonance (NMR) approach is introduced that enables real-time monitoring of the metabolism of Levodopa (L-dopa), an anti-Parkinson drug, in both live bacteria and bacteria-host (Caenorhabditis elegans) symbiotic systems. The quantitative method reveals that discrete Enterococcus faecalis substrains produce different amounts of dopamine in live hosts, even though they are a single species and all have the Tyrosine decarboxylase (TyrDC) gene involved in L-dopa metabolism. The differential bacterial metabolic activity correlates with differing Parkinson's molecular pathology concerning alpha-synuclein aggregation as well as behavioral phenotypes. The gene's existence or expression is not an indicator of metabolic activity is also shown, underscoring the significance of quantitative metabolic estimation in vivo. This simple approach is widely adaptable to any chemical drug to elucidate pharmacomicrobiomic relationships and may help rapidly screen bacterial metabolic effects in drug development.

논문정보

형식Research article
게재일2024년 07월 (BRIC 등록일 2024-07-30)
연구진국내 연구진
분야 생명과학 > 생화학

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