POLYKETIDE-DERIVED SECONDARY METABOLITES FROM DOTHIDEOMYCETES SP

Discovering alternative compounds for treating antibiotic-resistant infections is critical to alleviate the current antibiotic resistance crisis. Endophytic fungi are a source of numerous recently approved antibiotics particularly polyketide-derived molecules. This study aimed to isolate and identify antimicrobial compounds from Dothideomycetes sp. 11144 as well as molecular docking study for their affinity to different Methicillin-resistant Staphylococcus aureus (MRSA) selected proteins. Herein, we describe the isolation of four polyketide-type metabolites, a new naturalα-pyrone derivative, (R)-6-(2-hydroxypropyl)-4-methoxy-2H-pyran-2-one (1) along with three known anthraquinone derivatives, chrysophanol (2), emodin (3), and coniothyrinone B (4) from Dothideomycetes sp. 11144 liquid culture. The extracts and isolated compounds were screened for their antimicrobial activity. (R)-6-(2-hydroxypropyl)-4-methoxy-2H-pyran-2-one (1) and emodin (3) exhibited antibacterial activity against MRSA with IC50 values of 61.0 and 24.4µM, respectively. They were screened virtually via molecular docking for their affinity to different MRSA essential proteins compared to conventional inhibitors. Emodin demonstrated high affinity to the penicillin-binding protein with a pose score of-13.57 kcal/mol (1MWT). The emodin architecture could serve as a framework for the development of potent anti-MRSA antibiotics.