Rapid discovery of a new antifoulant: From in silico studies targeting barnacle chitin synthase to efficacy against barnacle settlement

• Published in: Ecotoxicology and environmental safety Vol. 274; p. 116187
• Main Authors: Wang, Zhixuan, Yao, Shanshan, Han, Zhaofang, Li, Zhuo, Wu, Zhiwen, Hao, Huanhuan, Feng, Danqing
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01-04-2024; Elsevier
• Subjects: Alkaloids - pharmacology; Animals; Antifoulant; Barnacle; Biofouling - prevention & control; Chitin synthase; Chitin Synthase - genetics; Chitin Synthase - metabolism; Computer-aided drug design; Larva; Marine biofouling; Marine natural products; Molecular Docking Simulation; Reproducibility of Results; Thoracica; Computer-aided drug design; Barnacle; Antifoulant; Chitin synthase; Marine biofouling; Marine natural products
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/j.ecoenv.2024.116187

Due to the adverse environmental impacts of toxic heavy metal–based antifoulants, the screening of environmentally friendly antifoulants has become important for the development of marine antifouling technology. Compared with the traditional lengthy and costly screening method, computer-aided drug design (CADD) offers a promising and efficient solution that can accelerate the screening process of green antifoulants. In this study, we selected barnacle chitin synthase (CHS, an important enzyme for barnacle settlement and development) as the target protein for docking screening. Three CHS genes were identified in the barnacle Amphibalanus amphitrite, and their encoded proteins were found to share a conserved glycosyltransferase domain. Molecular docking of 31,561 marine natural products with AaCHSs revealed that zoanthamine alkaloids had the best binding affinity (−11.8 to −12.6 kcal/mol) to AaCHSs. Considering that the low abundance of zoanthamine alkaloids in marine organisms would limit their application as antifoulants, a marine fungal–derived natural product, mycoepoxydiene (MED), which has a similar chemical structure to zoanthamine alkaloids and the potential for large-scale production by fermentation, was selected and validated for stable binding to AaCHS2L2 using molecular docking and molecular dynamics simulations. Finally, the efficacy of MED in inhibiting cyprid settlement of A. amphitrite was confirmed by a bioassay that demonstrated an EC50 of 1.97 μg/mL, suggesting its potential as an antifoulant candidate. Our research confirmed the reliability of using AaCHSs as antifouling targets and has provided insights for the efficient discovery of green antifoulants by CADD.
•CADD has the potential to accelerate the screening of eco-friendly antifoulants.•Zoanthamine alkaloids exhibit superior binding affinity to barnacle chitin synthase.•Mycoepoxydiene shows efficacy (EC50: 1.97 μg/mL) as an antifoulant candidate.