Acetaminophen-traces bioremediation with novel phenotypically and genotypically characterized 2 Streptomyces strains using chemo-informatics, in vivo, and in vitro experiments for cytotoxicity and biological activity

Abstract

We isolated two novel bacterial strains, active against the environmental pollutant acetaminophen/Paracetamol®. Streptomyces chrestomyceticus (symbol RS2) and Flavofuscus (symbol M33) collected from El-Natrun Valley, Egypt-water, sediment, and sand samples, taxonomically characterized using a transmission electron microscope (TEM). Genotypic identification, based on 16S rRNA gene sequence analysis followed by BLAST alignment, were deposited on the NCBI as 2 novel strains https://www.ncbi.nlm.nih.gov/nuccore/OM665324 and https://www.ncbi.nlm.nih.gov/nuccore/OM665325 . The phylogenetic tree was constructed. Acetaminophen secondary or intermediate product's chemical structure was identified by GC/LC MS. Some selected acetaminophen secondary-product extracts and derived compounds were examined against a panel of test micro-organisms and fortunately showed a good anti-microbial effect. In silico chemo-informatics Swiss ADMET evaluation was used in the selected bio-degradation extracts for absorption (gastric), distribution (to CNS), metabolism (hepatic), excretion (renal), and finally not toxic, being non-mutagenic/teratogenic or genotoxic, virtually. Moreover, in vitro cytotoxic activity of these selected bio-degradation secondary products was examined against HepG2 and MCF7 cancer cell lines, where M33 and RS2 extract effects on acetaminophen/paracetamol bio-degradation products were safe, with higher IC50 on HepG2 and MCF7 than the acetaminophen/paracetamol IC50 of 108.5 μg/ml. Moreover, an in vivo oral acute single-dose toxicity experiment was conducted, to confirm these in vitro and in silico lower toxicity (better safety) than acetaminophen/paracetamol.