Abstract
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.
Highlights
Microbial natural products, those produced by filamentous Actinobacteria, underpin the majority of clinically used antibiotics
Almost a century of research and industrial activity has earned Streptomyces species and other filamentous Actinobacteria a well-deserved reputation for their ability to produce a vast array of natural products, many of which have found utility in the clinic
It is not all doom and gloom, ; we are living in the “Genomics Age” of antibiotic discovery, which began in 2002 with the sequencing of the first Streptomyces genome, Streptomyces coelicolor A3(2) [3]
Summary
Those produced by filamentous Actinobacteria, underpin the majority of clinically used antibiotics. Analysis of this genome sequence identified a greater number of natural product biosynthetic gene clusters (BGCs) than the organism was known to produce. Perspective is relatively inactive in a laboratory setting, with most molecules detected in laboratory culture having been previously identified and linked to biosynthetic gene clusters (BGCs) (Known Knowns).
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