Novel Post-Translationally Modified Non-Ribosomal Peptides (Nrps) From The Ghanaian Streptomyces Sp. De2e

ABSTRACT

Non-ribosomal peptides (NRPs) are currently receiving considerable interests for possible development as effective alternatives to clinically failing conventional small molecule antibiotics. Particularly, NRPs produced by the genus Streptomyces have attracted considerable attention given the antibiotic production history of the genus. In this current report, a novel Ghanaian Streptomyces sp. strain DE2E isolated from the high biodiversity rich wetlands of the Brong-Ahafo Region of Ghana was thoroughly investigated for its capacity to produce bioactive NRPs. The total crude extract (TCE) obtained after harvesting the extracts of Streptomyces sp. DE2E in tryptic soy broth (TSBY) culture media was analyzed by spectroscopic and spectrometric techniques. Screening and dereplication processes involving the use of HRESI/HPLC-MSn data and AntiMarin database revealed the presence of large molecules which were found to be novel NRPs. A modified Kupchan solvent partitioning process of the TCE yielded four main fractions FH, FD, FM and WB amongst which the FD fraction was found to contain these large molecules. Sephadex LH-20 size exclusion chromatography fractionation produced the prioritized fraction SFB, which was subjected to HPLC to give five structurally related NRPs (peaks E–I). The proposed structure of the compound DE2E-TSBY-FD-SFB-I which was the largest among the five peptides isolated, was determined using 1D, 2D NMR interpretations and MSn data analysis. This compound was found to be a post-translationally modified NRPs macrocyclic pentapeptide whose structural confirmation will facilitate the subsequent determination of the remaining four other peptides. Biological screening of the compound DE2E-TSBY-FD-SFB-I showed strong antibacterial and antiparasitic activity against Shigella sonnei (IC50 = 10.01μM) and Trypanosoma brucei (IC50 = 12.89μM) respectively.