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揭示真菌次生代谢产物的宝库:从弗莱明的实验室到国际空间站。

Uncovering the repertoire of fungal secondary metabolites: From Fleming's laboratory to the International Space Station.

机构信息

a Lodz University of Technology , Faculty of Process and Environmental Engineering, Department of Bioprocess Engineering , Lodz , Poland.

出版信息

Bioengineered. 2018 Jan 1;9(1):12-16. doi: 10.1080/21655979.2017.1341022. Epub 2017 Jul 12.

DOI:10.1080/21655979.2017.1341022
PMID:28632991
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5972916/
Abstract

Fungi produce a variety of secondary metabolites (SMs), low-molecular weight compounds associated with many potentially useful biologic activities. The examples of biotechnologically relevant fungal metabolites include penicillin, a β-lactam antibiotic, and lovastatin, a cholesterol-lowering drug. The discovery of pharmaceutical lead compounds within the microbial metabolic pools relies on the selection and biochemical characterization of promising strains. Not all SMs are produced under standard cultivation conditions, hence the uncovering of chemical potential of investigated strains often requires the use of induction strategies to awake the associated biosynthetic genes. Triggering the secondary metabolic pathways can be achieved through the variation of cultivation conditions and growth media composition. The alternative strategy is to use genetic engineering to activate the respective genomic segments, e.g. by the manipulation of regulators or chromatin-modifying enzymes. Recently, whole-genome sequencing of several fungi isolated from the Chernobyl accident area was reported by Singh et al. (Genome Announc 2017; 5:e01602-16). These strains were selected for exposure to microgravity at the International Space Station. Biochemical characterization of fungi cultivated under extreme conditions is likely to provide valuable insights into the adaptation mechanism associated with metabolism and, possibly, a catalog of novel molecules of potential pharmaceutical importance.

摘要

真菌产生各种次生代谢物(SMs),这些低分子量化合物与许多潜在有用的生物活性有关。生物技术相关真菌代谢物的例子包括青霉素,一种β-内酰胺抗生素,和洛伐他汀,一种降低胆固醇的药物。在微生物代谢库中发现药物先导化合物依赖于有希望的菌株的选择和生化特性鉴定。并非所有的 SMs 都是在标准培养条件下产生的,因此,通常需要使用诱导策略来揭示被研究菌株的化学潜力,以唤醒相关的生物合成基因。触发次生代谢途径可以通过改变培养条件和生长介质的组成来实现。另一种策略是使用遗传工程来激活相应的基因组片段,例如通过操纵调节剂或染色质修饰酶。最近,Singh 等人报道了从切尔诺贝利事故地区分离出的几种真菌的全基因组测序结果(Genome Announc 2017; 5:e01602-16)。这些菌株被选中在国际空间站上暴露于微重力环境下。在极端条件下培养真菌的生化特性分析,可能会深入了解与代谢相关的适应机制,并且可能会发现一系列具有潜在药物重要性的新型分子。

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Genome Announc. 2017 Apr 13;5(15):e01602-16. doi: 10.1128/genomeA.01602-16.
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