The short history, specific features and future prospects of research of microbial metabolites, including antibiotics and other bioactive metabolites, are summarized. The microbial origin, diversity of producing species, functions and various bioactivities of metabolites, unique features of their chemical structures are discussed, mainly on the basis of statistical data. The possible numbers of metabolites may be discovered in the future, the problems of dereplication of newly isolated compounds as well as the new trends and prospects of the research are also discussed.

The declining trends in microbial metabolite and natural products research and the refocusing of this research area are discussed. Renewing natural products research requires inexhaustible natural resources, as well as new genetic techniques and microbial sources, including endophytic microbes. The numbers of known bioactive metabolites are summarized according to their microbiological origin, biological activities and chemical structures. Synthetic and natural product-based libraries are also compared. Importantly, the wide range of microbial metabolite bioactivities, future trends and the importance of prioritizing natural products over synthetic compounds are emphasized.

Antibiotics are essential for numerous medical procedures, including the treatment of bacterial infections, but their widespread use has led to the accumulation of resistance, prompting calls for the discovery of antibacterial agents with new targets. A majority of clinically approved antibacterial scaffolds are derived from microbial natural products, but these valuable molecules are not well annotated or organized, limiting the efficacy of modern informatic analyses. Here, we provide a comprehensive resource defining the targets, chemical origins and families of the natural antibacterial collective through a retrobiosynthetic algorithm. From this we also detail the directed mining of biosynthetic scaffolds and resistance determinants to reveal structures with a high likelihood of having previously unknown modes of action. Implementing this pipeline led to investigations of the telomycin family of natural products from Streptomyces canus, revealing that these bactericidal molecules possess a new antibacterial mode of action dependent on the bacterial phospholipid cardiolipin.

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