| Description |
Cyanobactins are N-to-C macrocyclic peptides that contain diverse modifications such as heterocyclization of Cys, Ser, or Thr, and isoprenylation of Ser, Thr, and Tyr. Although the above can be inferred to occur based on the final products, none of the enzymatic steps en route to cyanobactin biosynthesis had been characterized prior to this work. Indeed, until very recently, nothing at all was known about cyanobactin biosynthesis. Only after cloning and sequencing of the genetic elements required for cyanobactin biosynthesis was their biosynthetic origin deduced. Surprisingly, these complex natural products are biosynthesized by extensive posttranslational modification of ribosomally synthesized precursor peptides. As noted, these precursors are initially synthesized on the ribosome. Following ribosomal synthesis, various modifying enzymes carry out posttranslational modification of the aforementioned amino acids, as well as proteolysis of the precursor peptide to liberate 6-12 amino acid peptidyl groups, which are then macrocyclized. However, the manner in which the disparate genetic components required for cyanobactin biosynthesis functioned enzymatically to create these highly diverse and medicinally interesting compounds was unknown prior to this work. Herein the results of several studies that elucidate the steps en route to cyanobactin biosynthesis are described. The characterized steps include: N- and C-terminal proteolysis, macrocyclization, heterocyclization of Cys, Ser, and Thr, and prenylation of Ser, Thr and Tyr. |
