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.