Class of cyclic ribosomal peptide synthetic genes in filamentous fungi
Class of cyclic ribosomal peptide synthetic genes in filamentous fungi
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DOI：
10.1016/j.fgb.2015.12.010
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发表时间：
2016-01-01
影响因子：
3
通讯作者：
Asai, Kiyoshi
中科院分区：
文献类型：
--
作者：
Nagano, Nozomi;Umemura, Myco;Asai, Kiyoshi
最近发现的Ustiloxins是丝状真菌中核糖体合成的第一个环状肽基次级代谢产物。在这项工作中，两个功能未知的基因（ustYa/ustYb）的基因簇中的ustiloxins从黄曲霉被发现实验参与环化的肽。它们的同源基因主要存在于丝状真菌和蘑菇中。它们有两个可能形成活性位点的“HXXHC”基序。计算基因组分析表明，这些基因经常位于核糖体肽前体的候选基因附近，核糖体肽前体在N-末端具有信号肽，并且在丝状真菌，特别是黑曲霉的基因组中具有环状部分的核心肽的重复序列，如在ustiloxin基因簇中所观察到的。根据ustYa/ustYb同源基因和邻近的核糖体肽前体候选基因的组合，将计算鉴定的94个核糖体肽前体候选基因分为40多种类型，包括各种各样的核心肽序列。实验验证了一组预测的核糖体肽生物合成基因，以合成一种新的环状肽化合物，命名为Asperipin-2a，其包含与ustiloxin前体不同的相应前体基因中的氨基酸序列。(C)2015作者爱思唯尔公司出版
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. (C) 2015 The Authors. Published by Elsevier Inc.