Bioassay-Guided Fractionation Leads to the Detection of Cholic Acid Generated by the Rare Thalassomonas sp.

Abstract

Bacterial symbionts of marine invertebrates are rich sources of novel, pharmaceutically relevant natural products that could become leads in combatting multidrug-resistant pathogens and treating disease. In this study, the bioactive potential of the marine invertebrate symbiont Thalassomonas actiniarum was investigated. Bioactivity screening of the strain revealed Gram-positive specific antibacterial activity as well as cytotoxic activity against a human melanoma cell line (A2058). The dereplication of the active fraction using HPLC-MS led to the isolation and structural elucidation of cholic acid and 3-oxo cholic acid. T. actiniarum is one of three type species belonging to the genus Thalassomonas. The ability to generate cholic acid was assessed for all three species using thin-layer chromatography and was confirmed by LC-MS. The re-sequencing of all three Thalassomonas type species using long-read Oxford Nanopore Technology (ONT) and Illumina data produced complete genomes, enabling the bioinformatic assessment of the ability of the strains to produce cholic acid. Although a complete biosynthetic pathway for cholic acid synthesis in this genus could not be determined based on sequence-based homology searches, the identification of putative penicillin or homoserine lactone acylases in all three species suggests a mechanism for the hydrolysis of conjugated bile acids present in the growth medium, resulting in the generation of cholic acid and 3-oxo cholic acid. With little known currently about the bioactivities of this genus, this study serves as the foundation for future investigations into their bioactive potential as well as the potential ecological role of bile acid transformation, sterol modification and quorum quenching by Thalassomonas sp. in the marine environment.

Synthesis of Some New 1,3,4-Thiadiazole Derivatives Derived from Cholic Acid and Evaluation of their Biological Activity

“…A solution containing ten drops of glacial acetic acid and 0.01 mol of chlorobenzaldehyde in 15 mL of ethanol was added to a mixture containing 0.01 mol of compound (6) in ethanol (30 mL) and refluxed for 3 hrs when TLC revealed no starting material, the resultant solution is concentrated to half, the residue was then added to crushed ice. The product is filtered and washed with water to give a white solid, m.p.…”

“…Cholic acid with chenodeoxycholic acid, known as an important primary bile acid, is synthesized by cholesterol, and it is also produced in the liver. The concentration of these two acids is equal in humans, and they are converted to amino biliary acids (6). Figure (1) gives An illustration of intestinal bacteria further transforming deoxycholic acid and lithocholic acid, respectively, into biliary acid (7,8).…”