Discovery and Characterization of a PKS-NRPS Hybrid in Aspergillus terreus by Genome Mining

Discovery and Characterization of a PKS-NRPS Hybrid in Aspergillus terreus by Genome Mining
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DOI:
10.1021/acs.jnatprod.9b01140
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发表时间:
2020-02-01
影响因子:
5.1
通讯作者:
Lu, Xuefeng
Lu, Xuefeng
中科院分区:
生物学2区
文献类型:
--
作者:
Tang, Shen;Zhang, Wei;Lu, Xuefeng

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真菌聚酮合成酶-非核糖体肽合成酶(PKS-NRPS)杂种具有显著的结构特征和生物活性。本研究通过基因组挖掘在土曲霉中发现了一种PKS-NRPS杂交酶。通过激活簇特异性转录调控因子,成功激活了这一隐秘的PKS-NRPS基因簇,鉴定出10个产物(1-10)为pyranterreones。通过功能遗传学、生物信息学和同位素标记饲养分析,揭示了其生物合成途径。这是在地瓜中发现的第二个PKS-NRPS杂交种。
Fungal polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) hybrids have been characterized to produce polyketide amino acid compounds with striking structural features and biological activities. In this study, a PKS-NRPS hybrid enzyme was found in Aspergillus terreus by genome mining. By activating the cluster-specific transcriptional regulator, this cryptic PKS-NRPS gene cluster was successfully activated and ten products (1-10) were identified as pyranterreones. Using functional genetics, bioinformatics, and isotope-labeling feeding analysis, the biosynthetic pathway was revealed. This is the second PKS-NRPS hybrid identified in A. terreus.