Class of cyclic ribosomal peptide synthetic genes in filamentous fungi

• Published in: Fungal genetics and biology 2016-01, Vol.86, p.58-70
• Main Authors: Nagano, Nozomi, Umemura, Myco, Izumikawa, Miho, Kawano, Jin, Ishii, Tomoko, Kikuchi, Moto, Tomii, Kentaro, Kumagai, Toshitaka, Yoshimi, Akira, Machida, Masayuki, Abe, Keietsu, Shin-ya, Kazuo, Asai, Kiyoshi
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Aspergilli; Aspergillus flavus; Aspergillus flavus - genetics; Genes, Fungal; Genes, Synthetic; Genome analyses; Genome, Fungal; Molecular Sequence Data; Multigene Family; Peptides, Cyclic - chemistry; Peptides, Cyclic - genetics; Ribosomal peptide synthetic pathways; Ribosomes - metabolism; Secondary metabolites
• ISSN: 1087-1845; 1096-0937
• DOI: 10.1016/j.fgb.2015.12.010

•94 ustiloxin-like ribosomal peptide precursor genes were identified from Aspergilli.•Function-unknown ustYa and ustYb are likely involved in ustiloxin B cyclization.•Homologous genes to ustYa/Yb are observed mainly in Ascomycota and Basidiomycota.•The precursor genes are coupled with ustYa/Yb homologous genes on genomes.•One set of identified genes produces a newly identified bicyclic ribosomal peptide. Ustiloxins were found recently to be the first example of cyclic peptidyl secondary metabolites that are ribosomally synthesized in filamentous fungi. In this work, two function-unknown genes (ustYa/ustYb) in the gene cluster for ustiloxins from Aspergillus flavus were found experimentally to be involved in cyclization of the peptide. Their homologous genes are observed mainly in filamentous fungi and mushrooms. They have two “HXXHC” motifs that might form active sites. Computational genome analyses showed that these genes are frequently located near candidate genes for ribosomal peptide precursors, which have signal peptides at the N-termini and repeated sequences with core peptides for the cyclic portions, in the genomes of filamentous fungi, particularly Aspergilli, as observed in the ustiloxin gene cluster. Based on the combination of the ustYa/ustYb homologous genes and the nearby ribosomal peptide precursor candidate genes, 94 ribosomal peptide precursor candidates that were identified computationally from Aspergilli genome sequences were classified into more than 40 types including a wide variety of core peptide sequences. A set of the predicted ribosomal peptide biosynthetic genes was experimentally verified to synthesize a new cyclic peptide compound, designated as asperipin-2a, which comprises the amino acid sequence in the corresponding precursor gene, distinct from the ustiloxin precursors.