Fungal peptide synthetases: an update on functions and specificity signatures

• Fungi produce small-molecule peptides non-ribosomally via peptide synthetases.
• Non-canonical synthetases produce quinones or furanones.
• Substrate categories of synthetases can be anticipated.
• Specificity signatures for various substrates have been identified.

A considerable share of fungal small-molecule natural products is assembled via nonribosomal peptide synthetases (NRPSs). Here, we introduce the readers to two topical aspects which have emerged during work with enzymes of both asco- and basidiomycete origin. First, we highlight the function of non-canonical NRPS-like enzymes which lack the ability to make peptide bonds, and we summarize how they contribute to metabolic diversity. Second, we address the question to what extent substrates of fungal peptide synthetases and related enzymes can be predicted out of their primary sequence.