海洋来源节菱孢菌ZSDS1-F3中PKS-NRPS类天然产物挖掘

Discovery and characterization of a PKS-NRPS hybrid in Arthrinium arundinis ZSDS1-F3 by genome mining

摘要:

【目的】以基因组信息为指导，定向激活海洋来源真菌Arthrinium arundinis ZSDS1-F3中沉默的聚酮合成酶-非核糖体肽合成酶(PKS-NRPS)类生物合成基因簇，鉴定次级代谢产物结构。【方法】通过启动子工程和异源表达的策略激活实验室培养条件下沉默或低表达的生物合成基因簇，实现目标化合物的分离，通过HR-ESI-MS和NMR数据分析鉴定产物结构，结合基因重组和生物信息学分析结果推导化合物的生物合成途径。【结果】依据基因组生物信息学分析，从海洋来源真菌A.arundinis ZSDS1-F3中选取一个编码PKS-NRPS类次级代谢产物的生物合成基因簇开展研究，在宿主Aspergillus nidulansA1145中实现了基因簇的异源表达，从中分离到2个新化合物，并推导了其生物合成途径。【结论】基因组信息指导下的天然产物挖掘，可以目标明确地分离产物，加快真菌中新颖天然产物的发现步伐。

Abstract:

[Objective] To activate the biosynthesis gene cluster for polyketide synthases-nonribosomal peptide synthetases (PKS-NRPS) from the marine-derived Arthrinium arundinis ZSDS1-F3 based on genome analysis, and to isolate and identify the secondary metabolites. [Methods] The cryptic biosynthesis gene cluster was activated by promoter engineering and heterologous expression. The products were isolated and elucidated by HR-ESI-MS and 1D and 2D NMR, and the biosynthetic pathways of them were deduced based on gene recombination and bioinformatics analysis. [Results] A dormant PKS-NRPS-encoding gene cluster from A. arundinis ZSDS1-F3 was activated through heterologous expression in Aspergillus nidulans A1145. Two new products were isolated and the biosynthetic pathways were clarified. [Conclusion] Via bioinformatics analysis, genome mining plays an important role in the discovery of novel natural products from fungi.