The first antibiotic, salvarsan, was deployed in 1910. In just over 100 years antibiotics have drastically changed modern medicine and extended the average human lifespan by 23 years. The discovery of penicillin in 1928 started the golden age of natural product antibiotic discovery that peaked in the mid-1950s. Since then, a gradual decline in antibiotic discovery and development and the evolution of drug resistance in many human pathogens has led to the current antimicrobial resistance crisis. Here we give an overview of the history of antibiotic discovery, the major classes of antibiotics and where they come from. We argue that the future of antibiotic discovery looks bright as new technologies such as genome mining and editing are deployed to discover new natural products with diverse bioactivities. We also report on the current state of antibiotic development, with 45 drugs currently going through the clinical trials pipeline, including several new classes with novel modes of action that are in phase 3 clinical trials. Overall, there are promising signs for antibiotic discovery, but changes in financial models are required to translate scientific advances into clinically approved antibiotics.

Covering: 1988 to 2012 This review presents recommended nomenclature for the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs), a rapidly growing class of natural products. The current knowledge regarding the biosynthesis of the >20 distinct compound classes is also reviewed, and commonalities are discussed.

A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.

This review provides a comprehensive update of the advances in discovery, biosynthesis, and engineering of ribosomally-synthesized and post-translationally modified peptides (RiPPs).