Waste to Resource: Mining Antimicrobial Peptides in Sludge from Metagenomes Using Machine Learning

The emergence of antibiotic-resistant bacteria poses a huge threat to the treatment of infections. Antimicrobial peptides are a class of short peptides that widely exist in organisms and are considered as potential substitutes for traditional antibiotics. Here, we use metagenomics combined with machine learning to find antimicrobial peptides from environmental metagenomes and successfully obtained 16,044,909 predicted AMPs. We compared the abundance of potential antimicrobial peptides in natural environments and engineered environments, and found that engineered environments also have great potential. Further, we chose sludge as a typical engineered environmental sample, and tried to mine antimicrobial peptides from it. Through metaproteome analysis and correlation analysis, we mined 27 candidate AMPs from sludge. We successfully synthesized 25 peptides by chemical synthesis, and experimentally verified that 21 peptides had antibacterial activity against the 4 strains tested. Our work highlights the potential for mining new antimicrobial peptides from engineered environments and demonstrates the effectiveness of mining antimicrobial peptides from sludge.