Biosynthesis of Cyclochlorotine: Identification of the Genes Involved in Oxidative Transformations and Intramolecular <i>O</i>,<i>N</i>-Transacylation
Yulu Jiang, Taro Ozaki, Chengwei Liu, Yuya Igarashi, Ying Ye, Shoubin Tang, Tao Ye, Jun‐ichi Maruyama, Atsushi Minami, Hideaki Oikawa
Abstract
Mycotoxin cyclochlorotine (1) and structurally related astins are cyclic pentapeptides containing unique nonproteinogenic amino acids, such as β-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.