# Beta-lactamases

The functional diversity and mutational potential of beta-lactamases in environmental microbial communities were only partly understood. Combining protein language models with ensemble learning identified more than 46,000 putative beta-lactamases across all four Ambler classes from environmental metagenomes; two class C candidates sharing about 30% sequence identity with known enzymes conferred resistance to multiple beta-lactam antibiotics when expressed in E. coli, and mutations found by combining an inverse-folding model with protein language models altered resistance profiles, including increased carbapenem resistance.

The functional diversity and mutational potential of beta-lactamases in environmental microbial communities were only partly understood. Combining protein language models with ensemble learning identified more than 46,000 putative beta-lactamases across all four Ambler classes from environmental metagenomes; two class C candidates sharing about 30% sequence identity with known enzymes conferred resistance to multiple beta-lactam antibiotics when expressed in E. coli, and mutations found by combining an inverse-folding model with protein language models altered resistance profiles, including increased carbapenem resistance.