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从基因组学到代谢组学,朝着发现真菌次生代谢产物的综合策略迈进。

From genomics to metabolomics, moving toward an integrated strategy for the discovery of fungal secondary metabolites.

机构信息

Toxalim (Research Centre in Food Toxicology) Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, F-31027 Toulouse, France.

出版信息

Nat Prod Rep. 2018 Feb 21;35(2):147-173. doi: 10.1039/c7np00032d.

DOI:10.1039/c7np00032d
PMID:29384544
Abstract

Fungal secondary metabolites are defined by bioactive properties that ensure adaptation of the fungus to its environment. Although some of these natural products are promising sources of new lead compounds especially for the pharmaceutical industry, others pose risks to human and animal health. The identification of secondary metabolites is critical to assessing both the utility and risks of these compounds. Since fungi present biological specificities different from other microorganisms, this review covers the different strategies specifically used in fungal studies to perform this critical identification. Strategies focused on the direct detection of the secondary metabolites are firstly reported. Particularly, advances in high-throughput untargeted metabolomics have led to the generation of large datasets whose exploitation and interpretation generally require bioinformatics tools. Then, the genome-based methods used to study the entire fungal metabolic potential are reported. Transcriptomic and proteomic tools used in the discovery of fungal secondary metabolites are presented as links between genomic methods and metabolomic experiments. Finally, the influence of the culture environment on the synthesis of secondary metabolites by fungi is highlighted as a major factor to consider in research on fungal secondary metabolites. Through this review, we seek to emphasize that the discovery of natural products should integrate all of these valuable tools. Attention is also drawn to emerging technologies that will certainly revolutionize fungal research and to the use of computational tools that are necessary but whose results should be interpreted carefully.

摘要

真菌次生代谢产物的定义是具有生物活性的特性,这些特性确保了真菌对其环境的适应。虽然这些天然产物中的一些是很有前途的新药先导化合物的来源,特别是对制药行业而言,但其他一些则对人类和动物健康构成威胁。鉴定次生代谢产物对于评估这些化合物的用途和风险至关重要。由于真菌与其他微生物具有不同的生物学特性,因此,本文综述了专门用于真菌研究的不同策略,以进行这种关键的鉴定。首先报道了侧重于直接检测次生代谢产物的策略。特别是,高通量非靶向代谢组学的进展导致了大量数据集的产生,其开发和解释通常需要生物信息学工具。然后,报道了用于研究整个真菌代谢潜能的基于基因组的方法。转录组学和蛋白质组学工具在真菌次生代谢产物的发现中被用作基因组方法和代谢组学实验之间的联系。最后,强调了真菌培养环境对次生代谢产物合成的影响,这是真菌次生代谢产物研究中需要考虑的一个主要因素。通过本文综述,我们试图强调天然产物的发现应该整合所有这些有价值的工具。同时也注意到新兴技术将肯定会彻底改变真菌研究,以及计算工具的使用是必要的,但结果应该谨慎解释。

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