10.1021/acs.jnatprod.7b00903.s002 Shamima Nasrin Shamima Nasrin Suresh Ganji Suresh Ganji Kavita S. Kakirde Kavita S. Kakirde Melissa R. Jacob Melissa R. Jacob Mei Wang Mei Wang Ranga Rao Ravu Ranga Rao Ravu Paul A. Cobine Paul A. Cobine Ikhlas A. Khan Ikhlas A. Khan Cheng-Cang Wu Cheng-Cang Wu David A. Mead David A. Mead Xing-Cong Li Xing-Cong Li Mark R. Liles Mark R. Liles Chloramphenicol Derivatives with Antibacterial Activity Identified by Functional Metagenomics American Chemical Society 2018 methicillin-resistant Staphylococcus aureus MIC Twenty-seven clones soil-derived DNAs encoding inhibitors 1- p 3- butanoyl -1-propanoyl Cm Mycobacterium intracellulare Escherichia coli BAC clones 1- acetyl -3-propanoyl 1- acetyl -3-butanoyl metagenomic approach selectable antibiotic antibiotic activity metagenomic DNA soil library gene trfA Antibacterial Activity Identified Mycobacterium tuberculosis Functional Metagenomics LC-MS Chloramphenicol Derivatives MRSA plasmid copy induction 100 Kb chemical entities activity relationship studies 19 200 2018-06-13 13:21:50 Dataset https://acs.figshare.com/articles/dataset/Chloramphenicol_Derivatives_with_Antibacterial_Activity_Identified_by_Functional_Metagenomics/6509339 A functional metagenomic approach identified novel and diverse soil-derived DNAs encoding inhibitors to methicillin-resistant <i>Staphylococcus aureus</i> (MRSA). A metagenomic DNA soil library containing 19 200 recombinant <i>Escherichia coli</i> BAC clones with 100 Kb average insert size was screened for antibiotic activity. Twenty-seven clones inhibited MRSA, seven of which were found by LC-MS to possess modified chloramphenicol (<i>Cm</i>) derivatives, including three new compounds whose structures were established as 1-acetyl-3-propanoyl­chloramphenicol, 1-acetyl-3-butanoyl­chloramphenicol, and 3-butanoyl-1-propanoyl­chloramphenicol. <i>Cm</i> was used as the selectable antibiotic for cloning, suggesting that heterologously expressed enzymes resulted in derivatization of <i>Cm</i> into new chemical entities with biological activity. An esterase was found to be responsible for the enzymatic regeneration of <i>Cm</i>, and the gene <i>trfA</i> responsible for plasmid copy induction was found to be responsible for inducing antibacterial activity in some clones. Six additional acylchloramphenicols were synthesized for structure and antibacterial activity relationship studies, with 1-<i>p</i>-nitrobenzoyl­chloramphenicol the most active against <i>Mycobacterium intracellulare</i> and <i>Mycobacterium tuberculosis</i>, with MICs of 12.5 and 50.0 μg/mL, respectively.