Isolation and Characterization of Unusual Hydrazides from Streptomyces sp. Impact of the Cultivation Support and Extraction Procedure

Abstract

Three novel hydrazides, geralcins C-E (1-3), were isolated from Streptomyces sp. LMA-545, together with MH-031 and geralcins A and B. This unusual family of compounds was isolated from liquid-state and agar-supported fermentation using Amberlite XAD-16 solid-phase extraction during the cultivation step. The use of such neutral resin during the cultivation step allowed the specific adsorption of microbial secondary metabolites, avoiding any contamination of the crude extracts by the constituents of the culture medium. The trapped compounds were eluted from the resin with methanol, and their structures elucidated using (1)H, (13)C, and (15)N NMR spectroscopic analysis and high-resolution mass spectrometry. Molecular modeling calculations were applied in order to support structural attributions. No antimicrobial, cytotoxic, or DnaG-inhibition activities were detected for geralcins D and E. Geralcin C has no antimicrobial activity but exhibited an IC(50) of 0.8 μM against KB and HCT116 cancer cell lines. Furthermore, geralcin C inhibited the E. coli DnaG primase, a Gram-negative antimicrobial target, with an IC(50) of 0.7 mM.

Innovative Approach to Sustainable Marine Invertebrate Chemistry and a Scale-Up Technology for Open Marine Ecosystems

“…In general, we applied the in situ XAD-16 solid-phase extraction to microbial secondary metabolites. Among the many advantages of this method, it allows the isolation of the metabolic intermediates and the proposal of biosynthetic pathways [ 5 , 6 ].…”

DnaG Primase—A Target for the Development of Novel Antibacterial Agents

“…Phenolic monosaccharides (I & II) obtained from the methanolic extract of the Peruvian plant Polygonum cuspidatum were identified as inhibitors of the bacterial DNA primase enzyme with an IC 50 of 4 µM and 5 µM, respectively [ 112 ]. Other natural products known as cytosporone D [ 113 ] and geralcin C [ 114 ] were shown to inhibit DnaG primase of E. coli with an IC 50 of 250 µM [ 115 ] and 700 µM, respectively.…”

Impact of the Cultivation Technique on the Production of Secondary Metabolites by Chrysosporium lobatum TM-237-S5, Isolated from the Sponge Acanthella cavernosa

“…This certainly impacts their development steps and the expression of biosynthetic clusters of secondary metabolites because it is now well documented that, in fungi, secondary metabolism and life cycle among fungi are co-regulated at the genomic level [16][17][18].This idea drives us to compare the metabolic profile of fungi cultivated on a gar slants and in liquid state. The result is that solid-state cultivation often leads to larger molecular diversity than classical liquid state fermentation LSF [19][20][21]. The major obstacle that stands against agar cultivation is the scale-up.…”

“…This idea drives us to compare the metabolic profile of fungi cultivated on a gar slants and in liquid state. The result is that solid-state cultivation often leads to larger molecular diversity than classical liquid state fermentation LSF [19][20][21]. The major obstacle that stands against agar cultivation is the scale-up.…”