Cyclic peptide production using a macrocyclase with enhanced substrate promiscuity and relaxed recognition determinants

This project was supported by grants from the ERC (no. 339367, MJ), BBSRC IBCatalyst (no. BB/M028526/1, MJ, WEH), BBSRC FoF (no. BB/M013669/1, MJ, WEH), IBioIC Exemplar (no. 2014-2-4, MJ, WEH), an AstraZeneca studentship (MJ, WEH, LT, KR), the Academy of Finland (no. 259505, DPF) and the SULSA leaders award (WEH). The authors like to thank the Aberdeen Proteomics Facility and the Aberdeen School of Natural and Computing Sciences MS Facility for LCMS analysis. Electronic supplementary information (ESI) available: Experimental section, Fig. S1–S60 and Tables S1–S3. See DOI: 10.1039/c7cc05913bPeer reviewedPublisher PD

Antimicrobial analysis of honey against Staphylococcus aureus isolates from wound, ADMET properties of its bioactive compounds and in-silico evaluation against dihydropteroate synthase

One of the main challenges of wound healing is infection with multi-drug resistant (MDR) bacteria such as Staphylococcus aureus. The spectrum of antibiotics used to treat them is declining; thus, there is a need for alternatives. Our study was designed to evaluate the antimicrobial properties of honey, its pharmacokinetics (ADMET) properties and in-silico analysis of its bioactive compounds against dihydropteroate synthase of S. aureus using trimethoprim as control. Methods: Standard protocols were employed in collection and preparation of samples, generation of canonical strings, and conduction of microbiological analyses. Bioactive compounds’ ADMET properties were evaluated using the SWISSADME and the MCULE toxicity checker tools. The MCULE one-click docking tool was used in carrying out the dockings. Results: The gas chromatography-mass spectrophotometry revealed twenty (20) bioactive compounds and was dominated by sugars (> 60%). We isolated a total of 47 S. aureus isolates from the wound samples. At lower concentrations, resistance to trimethoprim (95.74 to 100.00%) was higher than honey (70.21 to 96.36%). Only seven (7) isolates meet Lipinski’s rule of five and ADMET properties. The docking scores of the bioactive compounds ranged from -3.3 to -4.6 while that of trimethoprim was -6.1, indicating better binding or interaction with the dihydropteroate synthase. The bioactive compounds were not substrates to P450 cytochrome enzymes (CYP1A2, CYP2CI9 and CYP2D6) and p glycoprotein, indicating better gastrointestinal tract (GIT) absorption. Conclusion: The favourable docking properties shown by the bioactive compounds suggest they could be lead compounds for newer antimetabolites for management of MDR S. aureus