Bacteria make a meal of penicillin

Somewhere in the soil microbiome, bacteria are chowing down on penicillin and other β-lactam antibiotics. A team of researchers led by Gautam Dantas of Washington University in St. Louis provides evidence for a pathway those bacteria might use to incorporate β-lactams into the microbes’ central metabolism (Nat. Chem. Biol. 2018, DOI: 10.1038/s41589-018-0052-1). After genomic and transcriptomic analysis of bacterial strains that can survive using penicillin as their sole carbon source, the researchers propose that the bacteria first cleave the β-lactam ring to produce benzylpenicilloic acid. That compound acts as a substrate for an amidase enzyme, which hydrolyzes the amide bond to release the phenylacetic acid side chain. Phenylacetic acid can be metabolized into acetyl-CoA and succinyl-CoA, which feed into the bacteria’s central metabolism. The researchers engineered a set of these penicillin-processing enzymes into Escherichia coli, creating a strain that subsists on penicillin as its sole carbon source. They propose that such engineered bacteria might be used for bioremediation of antibiotic-contaminated soils. But the researchers acknowledge that such bioremediation comes with the risk of spreading the resistance and degradation genes to other organisms.