Analysis of the genome of a Pseudomonas monsensis isolate that produces the antifungal dipeptide maculosin.

Candida species have been attributed to causing ~647,000 deaths annually. Candida albicans has been identified by the WHO as a priority pathogen for targeted antifungal drug development. To this end, we have screened microbial strains from the public outreach project Swab and Send for anti-Candida activity. This process identified Pseudomonas sp. SS1954.14, which displayed potent activity against C. albicans, both on agar and in a cell-free supernatant assay. Whole-genome sequence analysis identified this strain as Pseudomonas monsensis. It contains several biosynthetic gene clusters, suggesting that it can produce hydrogen cyanide, lokisin, pyoverdine and colicin/carocin, which may contribute to the observed antifungal activity. However, an active compound was separated by preparative high-performance liquid chromatography and identified through high-resolution mass spectrometry as maculosin [cyclo(Pro-Tyr)]. This cyclic dipeptide has previously been found to possess antifungal activity, but the exact biosynthetic mechanism remains undetermined. Reporting this genome alongside the associated evidence of maculosin production represents a valuable resource for biosynthetic investigations.