Ribosomal peptide biosynthetic pathways widely conserved in filamentous fungi

Recently, the biosynthetic gene cluster for ustiloxin B was identified in Aspergillus flavus, as the first example of ribosomal peptide biosynthetic pathways in Ascomycetes [1,2]. This type of secondary metabolic pathway harbours a gene coding a precursor protein for the compound backbone, which is generally cyclised and modified after translation. In the case of ustiloxin B, the precursor protein is processed by KexB protease in Golgi apparatus [3] and modified into the final form through five enzyme reactions in the pathway after cyclisation [4]. The ustiloxin pathway is prominent in its highly repeated core peptides and its genes of function-unknown but essential to the biosynthesis. In silico genome mining based on these characteristics revealed that this ustiloxin-type ribosomal peptide synthesis (ust-RiPS) pathway is widely conserved in Aspergilli and some other filamentous fungi, and their core peptide sequences were classified into more than 40 types [5]. Subsequent experimental compound exploration in culture accompanied with gene deletion resulted in a discovery of a novel cyclic peptide, asperipin-2a, from A. flavus [5]. This result implies that the ust-RiPS pathway is a promising resource for cyclic peptide synthesis.

[1] Umemura et al., Plos One, 8:e84028 (2013)
[2] Umemura et al., Fungal Genetics and Biology, 68, 23-30 (2014)
[3] Yoshimi et al., AMB Express, 6:9-16 (2016)
[4] Ye et al., Angewandte Chemie International Edition, in press
[5] Nagano et al., Fungal Genetics and Biology, 86:58-70 (2016)