Structure Determination And Bioactivity Of Novel Chlorinated Peptides Isolated From Rhodococcus Sp. M1042

Abstract

The Rhodococcus sp. M1042 is a new microbial strain that was isolated from soil sediments collected from Munzur Valley in Tunceli, Turkey. Species in this genus have been found to harbour extensive secondary metabolic pathways that produce novel metabolites with bioactivity with industrial and environmental bio-applications. The complete genome sequence of this strain contains 5,948,800 mega base pairs with 230 NRPS, PKS and NRPS-PKS gene clusters, some of which have been identified to produce already known bioactive compounds. The total crude extract (TCE) obtained after harvesting the fermentation broth of the Rhodococcus sp. M1042 was analysed by spectroscopic and spectrometric techniques to reveal the presence of three chlorinated peptides. A Kupchan solvent partitioning process, gave four fractions amongst which the WB fraction was found to contain these chlorinated peptides. Using column chromatography by gravity, Sephadex LH20 size exclusion and normal phase thin layer chromatography followed by HPLC led to the isolation and purification of these three peptides. The structure of one of the three chlorinated peptides was determined by 1D and 2D NMR data interpretations and mass spectrometry. The structure determination of the remaining two peptides is currently in progress. Subsequently, a connection is being made to the gene clusters that are responsible for the biosynthesis of these peptides. One of the compounds was tested for antiparasitic activity against Leishmania donovani, Trypanosoma brucei, Trichomonas mobilensi, and Plasmodium falciparum but was found to show minimal activity with IC50 >100 μM. The antibacterial activity against Gram-positive S. aureus ATCC 25923, the Gram-negative E. coli ATCC 25922 and a panel of clinical isolates of methicillin-resistant S. aureus (MRSA) strains are currently in progress.