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.

译文

真菌产生多种次级代谢产物 (SMs),与许多潜在有用的生物活性相关的低分子量化合物。与生物技术相关的真菌代谢物的例子包括青霉素,β-内酰胺抗生素和降低胆固醇的药物洛伐他汀。在微生物代谢池中发现药物先导化合物取决于有前途的菌株的选择和生化表征。并非所有SMs都是在标准培养条件下产生的,因此,发现所研究菌株的化学势通常需要使用诱导策略来唤醒相关的生物合成基因。通过改变培养条件和生长培养基组成,可以触发次级代谢途径。替代策略是使用基因工程来激活相应的基因组片段,例如通过调节因子或染色质修饰酶的操作。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 (genome announsc 2017; 5:e01602-16)。这些菌株被选择用于在国际空间站暴露于微重力下。在极端条件下培养的真菌的生化表征可能会为与代谢相关的适应机制以及可能具有潜在药物重要性的新型分子目录提供有价值的见解。

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