加拿大麦克马斯特大学Gerard D. Wright研究组发现，可以通过对常见抗生素基因簇的灭活来鉴别放线菌中隐藏的抗生素。该研究2019年9月9日在线发表在《自然—生物技术》上。

他们用CRISPR-Cas9基因组工程技术，敲除11种放线菌菌株中编码两种最常被重复使用的抗生素，链霉菌素或链霉素的基因。研究报告说，这种简单的方法将产生不同的抗生素，否则这些抗生素会被掩盖。他们能够快速发现罕见的和以前未知的抗生素变种，包括硫代乳霉素，阿米西汀，菲替罗菌素和5-氯-3-甲酰基吲哚。该策略可应用于现有菌株的收集以实现其生物合成潜力。

据介绍，放线菌是最大的细菌门之一，占土壤微生物群的13％至30％，是临床使用的抗生素种类的主要来源。在筛选抗微生物制剂时，多达50％的放线菌菌株被丢弃，因为它们产生已知的抗生素类型。尽管每种菌株可能具有产生多种化合物的能力，但由于已经表征的抗生素可能干扰新发现的化合物的筛选或纯化，因此菌株被丢弃。

附：英文原文

Title: Hidden antibiotics in actinomycetes can be identified by inactivation of gene clusters for common antibiotics

Author: Elizabeth J. Culp, Grace Yim, Nicholas Waglechner, Wenliang Wang, Andrew C. Pawlowski, Gerard D. Wright

Issue&Volume: 2019-09-09

Abstract: Actinobacteria, which are one of the largest bacterial phyla and comprise between 13 and 30% of the soil microbiota, are the main source of antibiotic classes in clinical use1. During screens for antimicrobials, as many as 50% of actinomycete strains are discarded because they produce a known antibiotic (Supplementary Fig. 1) (ref. 2). Despite each strain likely having the capacity to produce many compounds, strains are abandoned because the already characterized antibiotic could interfere with screening for, or purification of, newly discovered compounds3. We applied CRISPR-Cas9 genome engineering to knockout genes encoding two of the most frequently rediscovered antibiotics, streptothricin or streptomycin, in 11 actinomycete strains. We report that this simple approach led to production of different antibiotics that were otherwise masked. We were able to rapidly discover rare and previously unknown variants of antibiotics including thiolactomycin, amicetin, phenanthroviridin and 5-chloro-3-formylindole. This strategy could be applied to existing strain collections to realize their biosynthetic potential. Dereplication by inactivation of antibiotic production clusters in actinomycetes enables antibiotic discovery.

DOI: 10.1038/s41587-019-0241-9

Source:https://www.nature.com/articles/s41587-019-0241-9