Discovery of caerulomycin/collismycin-type 2,2-bipyridine natural products in the genomic era

2,2-Bipyridine (2,2-BP) is the unique molecular scaffold of the bioactive natural products represented by caerulomycins (CAEs) and collismycins (COLs). CAEs and COLs are highly similar in the chemical structures in which their 2,2-BP cores typically contain a di- or tri-substituted ring A and an unmodified ring B. Here, we summarize the CAE and COL-type 2,2-BP natural products known or hypothesized to date: (1) isolated using methods traditional for natural product characterization, (2) created by engineering the biosynthetic pathways of CAEs or COLs, and (3) predicted upon bioinformatics-guided genome mining. The identification of these CAE and COL-type 2,2-BP natural products not only demonstrates the development of research techniques and methods in the field of natural product chemistry but also reflects the general interest in the discovery of CAE and COL-type 2,2-BP natural products.