Natural and engineered cyclodipeptides: Biosynthesis, chemical diversity, and engineering strategies for diversification and high-yield bioproduction.

Cyclodipeptides are diverse chemical scaffolds that show a broad range of bioactivities relevant for medicine, agriculture, catalysis, and material sciences. can be synthesized enzymatically through two unrelated enzyme families, non-ribosomal peptide synthetases (NRPS) cyclodipeptide synthases (CDPSs). The diversity cyclodipeptides is derived from the amino acid side chains modification those side-chains by tailoring enzymes. While large spectrum already known today, additional space - as such potential new could accessed exploring yet undiscovered NRPS CDPS gene clusters well via engineering. Further, to exploit applications, low yield natural biosynthesis needs overcome. In this review we summarize current knowledge on CDPS-based biosynthesis, engineering approaches further strategies high-yield production cyclodipeptides, including discussion how advancements in synthetic biology metabolic accelerate translational cyclodipeptides.