Complex Interplay and Catalytic Versatility of Tailoring Enzymes for Efficient and Selective Biosynthesis of Fungal Mycotoxins

Mycotoxins have substantial impacts on agricultural production and food preservation. Some have high similarities in bioactivity but subtle differences on structures from various fungal producers. Understanding of their complex cross-biosynthesis will provide new insights into enzyme functions and food safety. Here, based on structurally related mycotoxins, such as aurovertins, asteltoxin, and citreoviridin, we showed that methyltransferase (MT)-catalyzed methylation is required for efficient oxidation and polyketide stability. MTs have broad interactions with polyketide synthases and flavin-containing monooxygenases (FMOs), while MT AstB is required for FMO AstC functionality in vivo. FMOs have common catalysis on pyrone-polyene intermediates but different catalytic specificity and efficiency on oxidative intermediates for the selective production of more toxic and complex mycotoxins. Thus, the subtle protein interaction and elaborate versatile catalysis of biosynthetic enzymes contribute to the efficient and selective biosynthesis of these structure-related mycotoxins and provide the basis to re-evaluate and control mycotoxins for agricultural and food safety.

Automated summary

Mycotoxins have significant impacts on agriculture and food safety. The study of structurally related mycotoxins provides new insights into enzyme functions and food safety. Methyltransferase-catalyzed methylation is necessary for efficient oxidation and polyketide stability. Methyltransferases interact with polyketide synthases and flavin-containing monooxygenases, and the protein interaction and versatile catalysis of these biosynthetic enzymes contribute to the efficient and selective biosynthesis of mycotoxins.