Cryptic or silent? The known unknowns, unknown knowns, and unknown unknowns of secondary metabolism

Paul A. Hoskisson, Ryan F. Seipke*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)
32 Downloads (Pure)


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.

Original languageEnglish
Article numbere02642-20
Number of pages5
Issue number5
Publication statusPublished - 20 Oct 2020


  • actinobacteria
  • natural products
  • secondary metabolism
  • specialized metabolism
  • streptomyces


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