Exploring the Pharmacological Potential of Kaurenoic Acid Produced via Synthetic Biology
Pimentel, L. L.; Teixeira, F. S.; Soares, A. M. S.; Costa, P. T.; Fontes, A. L.; Vidigal, S.; Pintado, M.; Rodriguez-Alcala, L. M.
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BackgroundKaurenoic acid (KA) is a bioactive diterpenoid commonly found in traditional medicinal plants such as Copaifera species, widely used in Amazonian ethnomedicine for its anti-inflammatory and antimicrobial properties. However, the sustainable supply of KA is limited due to environmental pressures and its complex extraction process from natural sources. Synthetic biology presents an innovative solution for producing KA, potentially reducing environmental impact while maintaining its traditional medicinal value. Aim of the studyThis work discusses the potential bioactive properties of kaurenoic acid (KA) obtained through synthetic biology. While ethnopharmacological studies have highlighted the anti-inflammatory and antimicrobial effects of plant extracts containing KA, limited research has focused on the pure compound due to its cost and limited availability. Materials and methodsThe study employed quantitative structure-activity relationship (QSAR) modeling and in vitro assays to investigate the anti-inflammatory and antimicrobial activities of S-KA and KNa. Physicochemical characterization, including Fourier transform infrared spectroscopy (FTIR-ATR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD), was conducted to compare structural properties and purity with G-KA. Additionally, solubility studies were performed across various solvents to assess the potential for different bioapplications. ResultsPurity assessments revealed 99.06% for S-KA versus 98.83% for a commercial standard. In silico calculations indicated that KA is hydrophobic. Solubility tests prompted the synthesis of a sodium salt derivative (KNa), increasing water solubility. Experimental evaluations demonstrated that S-KA and KNa exhibited similar (IL-6, IL-8) anti-inflammatory activity compared to betamethasone, and growth inhibition was observed against Staphylococcus aureus and Staphylococcus epidermidis. ConclusionThese findings highlight that kaurenoic acid from fermentation offers a sustainable alternative to naturally sourced KA with comparable bioactivity. The sodium salt derivative (KNa) enhances water solubility, expanding its potential for pharmacological applications. This study highlights the relevance of synthetic biology in preserving traditional medicinal knowledge while promoting environmental sustainability.
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