Unveiling the potential of bacterial keratinase with antiacne drugs for cosmeceutical applications: an in silico evaluation

Abstract

The keratinase serves as a catalyst with potential application in various industries, including textiles, leather, pharmaceuticals, cosmetics, and biotechnological applications. Previous studies have predominantly focused on fungal keratinase; however, our present work focuses on bacterial keratinase only. The novelty of using bacterial keratinase over fungal keratinase is because of its faster enzymatic activity, broader substrate specificity, increased stability and cost-effective production, making it efficient and adaptable for industrial applications. However, our present research investigates bacterial keratinase through in silico structural (physicochemical properties, primary, secondary, and tertiary structures) as well as functional analyses (protein–protein interaction networks, subcellular localization, and domain/motif presence), coupled with molecular docking against standard anti-acne drugs in use (adapalene, erythromycin, tretinoin, isotretinoin, and benzoyl peroxide). In this study, two bacterial keratinases, one from mesophilic Pseudomonas aeruginosa (6FZX) and another from thermophilic Meiothermus taiwanensis WR-220 (5WSL) have been studied to demonstrate comparative structural stability and functional activity. These enzymes are intracellular, facilitating proteolysis with metalloendopeptidase activity. Notably, keratinase exhibited a strong binding affinity for adapalene (binding energies of − 8.5 kcal/mol and − 9.6 kcal/mol for 5WSL and 6FZX, respectively) and lowest affinity to erythromycin (binding energy − 6.4 kcal/mol and − 5.9 kcal/mol for 5WSL and 6FZX respectively) among other studied anti-acne drugs like, tretinoin, isotretinoin, and benzoyl peroxide. In the case of de novo designing of anti-acne compounds, enhanced binding affinities are the key factor for selection of potential components. Our in silico analyses indicate that thermophilic keratinase displays better structural stability and functionality, particularly under high pH and high-temperature conditions, making it a promising candidate for cosmeceutical applications. Thermophilic keratinase may effectively operate in demanding skin environments and may offer advantages over mesophilic keratinase. These insights from comparative computational analysis will pave the way for further wet lab validation and industrial experiments to guide the selection of optimal candidates in antiacne formulations.