Engineered biosynthesis of thaxtomin phytotoxins

Herbicide-resistant weeds are a growing problem worldwide. Thaxtomin phytotoxins are a group of nitrated diketopiperazines produced by the potato common scab-causing pathogen Streptomyces scabies and other actinobacterial plant pathogens. They represent a unique class of microbial natural products with distinctive structural features and promising herbicidal activity. The biosynthesis of thaxtomins proceeds through multiple steps of unusual enzymatic reactions. Advances in understanding of thaxtomins biosynthetic machinery have provided the basis for precursor-directed biosynthesis, pathway refactoring, and one-pot biocombinatorial synthesis to generate thaxtomin analogues. We herein summarize recent findings on the biosynthesis of thaxtomins and highlight recent advances in the rational generation of novel thaxtomins for the development of potent herbicidal agents.