Cryptic or Silent? The Known Unknowns, Unknown Knowns, and Unknown Unknowns of Secondary Metabolism.
Cryptic or Silent? The Known Unknowns, Unknown Knowns, and Unknown Unknowns of Secondary Metabolism.
复制标题
DOI：
10.1128/mbio.02642-20
复制
发表时间：
2020-10-20
期刊：
影响因子：
6.4
通讯作者：
Seipke RF
中科院分区：
文献类型：
--
作者：
Hoskisson PA;Seipke RF
微生物天然产物，特别是丝状放线菌产生的那些，是大多数临床使用的抗生素的基础。不幸的是，自20世纪70年代以来，只发现了几种新的抗生素，这加剧了人们对抗生素失去效用的后世界末日的担忧。令人兴奋的是，基因组测序革命描绘了一幅全新的画面，其中丝状放线菌的平均菌株拥有20到50个天然产物生物合成途径，但在实验室条件下表达的很少。微生物天然产物，特别是丝状放线菌产生的那些，是大多数临床使用的抗生素的基础。不幸的是，自20世纪70年代以来，只发现了几种新的抗生素，这加剧了人们对抗生素失去效用的后世界末日的担忧。令人兴奋的是，基因组测序革命描绘了一幅全新的画面，其中丝状放线菌的平均菌株拥有20到50个天然产物生物合成途径，但在实验室条件下表达的很少。开发获得这种“隐藏的”生物化学多样性的方法有可能迎来抗生素发现的第二个黄金时代。基因组数据的激增导致在提及通过生物信息学分析鉴定的生物合成基因簇时不一致地使用“隐蔽的”和“沉默的”。在这个角度来看，我们讨论这个问题，并建议正式使用这个术语。
Microbial natural products, particularly those produced by filamentous Actinobacteria, underpin the majority of clinically used antibiotics. Unfortunately, only a few new antibiotic classes have been discovered since the 1970s, which has exacerbated fears of a postapocalyptic world in which antibiotics have lost their utility. Excitingly, the genome sequencing revolution painted an entirely new picture, one in which an average strain of filamentous Actinobacteria harbors 20 to 50 natural product biosynthetic pathways but expresses very few of these under laboratory conditions. Microbial natural products, particularly those produced by filamentous Actinobacteria, underpin the majority of clinically used antibiotics. Unfortunately, only a few new antibiotic classes have been discovered since the 1970s, which has exacerbated fears of a postapocalyptic world in which antibiotics have lost their utility. Excitingly, the genome sequencing revolution painted an entirely new picture, one in which an average strain of filamentous Actinobacteria harbors 20 to 50 natural product biosynthetic pathways but expresses very few of these under laboratory conditions. Development of methodology to access this “hidden” biochemical diversity has the potential to usher in a second Golden Era of antibiotic discovery. The proliferation of genomic data has led to inconsistent use of “cryptic” and “silent” when referring to biosynthetic gene clusters identified by bioinformatic analysis. In this Perspective, we discuss this issue and propose to formalize the use of this terminology.