Work

Microbial Biotransformation of the Sesquiterpene Carotol: Generation of Hydroxylated Metabolites with Potential Cytotoxic and Target-Specific Binding Activities

Year: 2025

Type: article

Abstract: Background Carotol, a major sesquiterpene alcohol found in carrot essential oil, exhibits promising biological activities including cytotoxic effects against various cancer cell lines. Despite its bioactivity, the metabolic fate and biotransformation pathways of carotol remain largely unexplored, particularly through microbial systems that can offer novel insights into its structural modifications and potential pharmacological applications. Results In this study, seventeen microbial strains were screened for their ability to biotransform carotol, with Absidia coerulea ATCC 6647 identified as the most effective strain. Preparative-scale fermentation using this strain led to the isolation and purification of three metabolites (CM1, CM2, and CM3). Spectroscopic analysis, including 1D and 2D NMR, HRMS, and single crystal X-ray diffraction, elucidated the structures of these metabolites as 9α-hydroxydaucol (CM1), 9α,13-dihydroxydaucol (CM2), and a diol derivative of daucol (CM3). Cytotoxicity evaluation against human liver (HepG-2), colon (HCT-116), breast (MCF-7), and lung (A-549) carcinoma cell lines, alongside normal lung fibroblasts (MRC-5), revealed that carotol exhibited the highest anticancer activity followed by CM2, CM3, and CM1. Molecular docking studies against human NADPH oxidase demonstrated that carotol and CM2 have stronger binding affinities and more stable interactions compared to the other metabolites, suggesting NADPH oxidase inhibition as a possible mechanism for their anticancer effects. Conclusion This study provides the first comprehensive microbial biotransformation pathway for carotol, leading to the identification of novel hydroxylated metabolites with varying cytotoxic activities. The findings highlight the potential of Absidia coerulea as a biocatalyst for producing bioactive carotol derivatives and underscore the relevance of NADPH oxidase inhibition in their anticancer mechanism. These results lay a foundation for future pharmacokinetic and drug development research involving carotol and its metabolites.

Source: Biomolecules

DOI: 10.3390/biom15121651

Authors: Hanan G. Sary, Mohammed A. Khedr, Mohamed M. Radwan, Mickey Vinodh, Abbas Ali, Khaled Y. Orabi

Institutions: Ain Shams University, Kuwait University, Helwan University, University of Mississippi

Language: English

Topic: Biochemical and biochemical processes

Subfield: Biotechnology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,258