Biosynthesis of Cyclochlorotine: Identification of the Genes Involved in Oxidative Transformations and Intramolecular O,N-Transacylation

Mycotoxin cyclochlorotine (1) and structurally related astins are cyclic pentapeptides containing unique nonproteinogenic amino acids, such as beta-phenylalanine, L-allo-threonine, and 3,4-dichloroproline. Herein, we report the biosynthetic pathway for 1, which involves intriguing tailoring processes mediated by DUF3328 proteins, including stereo- and regiospecific chlorination and hydroxylation and intramolecular O,N-transacylation. Our findings demonstrate that DUF3328 proteins, which are known to be involved in oxidative cyclization of fungal ribosomal peptides, have much higher functional diversity than previously expected.

Automated summary

In the biosynthetic pathway of mycotoxin cyclochlorotine, DUF3328 proteins mediate various tailoring processes, including chlorination and hydroxylation, demonstrating a much higher functional diversity than previously expected.