Microbial metabolism marvels: a comprehensive review of microbial drug transformation capabilities

Abstract

This comprehensive review elucidates the pivotal role of microbes in drug metabolism, synthesizing insights from an exhaustive analysis of over two hundred papers. Employing a structural classification system grounded in drug atom involvement, the review categorizes the microbiome-mediated drug-metabolizing capabilities of over 80 drugs. Additionally, it compiles pharmacodynamic and enzymatic details related to these reactions, striving to include information on encoding genes and specific involved microorganisms. Bridging biochemistry, pharmacology, genetics, and microbiology, this review not only serves to consolidate diverse research fields but also highlights the potential impact of microbial drug metabolism on future drug design and in silico studies. With a visionary outlook, it also lays the groundwork for personalized medicine interventions, emphasizing the importance of interdisciplinary collaboration for advancing drug development and enhancing therapeutic strategies.

Keywords: Gut microbiome; microbial drug metabolism; microbiota.

Figure 1.

Microbial drug metabolizing reactions involving a C-C bond.

Figure 2.

Microbial drug metabolizing reactions involving an amide bond. *β-lactamases activity varies from drug to drug. 2A shows only the core structures of drugs that can be modified by β-lactamases.

Figure 3.

Microbial drug metabolising reactions involving C-N bonds.

Figure 4.

Microbial drug metabolizing reactions involving C-O and C-S bonds. *epimerase activity shown in the picture represents the 7-epimerases acting on cholic acid and the 20-epimerase acting on cortisol. Other epimerases are known to act on hydroxy residues attached to carbon 3,12,17, and 20 of different steroid compounds.

Figure 5.

Microbial drug metabolizing reactions involving N-N and N-O bonds.

Figure 6.

Microbial drug metabolizing reactions involving S-O, P-O bonds, and conjugations.