Bacteria from the environments with complex ecology are the Nature’s cornucopia for secondary metabolites, most importantly antibiotics. These are organisms belonging to the phyla Actinomycetota, Bacillota, Myxococcota, and Cyanobacteriota, co-existing, communicating, and competing in soil and aquatic biotopes. Such interactions are indeed mediated with secondary metabolites. Biosynthesis of secondary metabolites is complex, involving multiple enzymes and assembly lines, known to be encoded within large biosynthetic gene clusters (BGCs). In fact, there are actually multiple BGCs in genome per average, while only few of them are actively expressed leading to the production of secondary metabolites. Advances in tools for in vivo, in vitro and in silico analyses in post-genomic era allows to investigate the biosynthesis of secondary metabolites in an unprecedented detail, bringing the problem to an interface of genomics, genetics, other biological disciplines, and advanced analytical chemistry. The investigation of secondary metabolites not only expands our understanding of bacterial ecology and their intricate interactions but also enables us to harness their therapeutic potential, develop new drugs, and combat the growing threat of antibiotic resistance.

In the current Topic, we aim to assemble a collection of papers that will showcase the latest advances in the field of natural bacterial products. This includes: (a) the discovery and description of non-ribosomal peptides, ribosomally synthesized and post-translationally modified peptides (RiPPs), polyketides, glycosides, and other natural products; (b) the investigation of the exact biosynthetic steps and mechanisms leading to the production of natural products at the gene and protein level; (c) the generation of novel derivatives of natural products through combinatorial biosynthesis or chemical modification; (d) the in silico prediction of biosynthetic pathways and comparative genomics of secondary metabolism. These aspects are important as they contribute to the general knowledge of bacterial bioactive secondary metabolites, paving the way for their future applications. We believe that Frontiers in Chemical Biology will become an important platform for publishing such research works in the near future, and this current topic will draw attention to this newly launched journal.

In this Research Topic we invite submissions addressing, but not limited to, the following themes:

· Novel bacterial secondary metabolites, especially antibiotics, or derivatives of natural products generated by combinatorial biosynthesis or other rational approaches;

· Correlating the senso lato secondary metabolome of an organisms with its genomic potential to produce natural products;

· Activation of silent biosynthetic pathways for cryptic or known secondary metabolites using different approaches;

· Investigation of the particular steps in the biosynthesis of secondary metabolites, either in vivo or in vitro;

· Interplay between the production of secondary metabolites with the nutritional and genetic factors governing/limiting the production;

· New methods for the analysis of bacterial secondary metabolites;

· Comparative genomics of secondary metabolism aimed to demonstrate how BGCs or their components emerge or evolve.

Dr. Sergey B. Zotchev and Dr. Susanne Schneiker-Bekel hold patents related to the Research Topic. All other members of the Editorial Team declare no competing interests.

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