Exploitation of the Streptomyces coelicolor A3(2) genome sequence for discovery of new natural products and biosynthetic pathways

Abstract

Streptomyces, and related genera of Actinobacteria, are renowned for their ability to produce antibiotics and other bioactive natural products with a wide range of applications in medicine and agriculture. Streptomyces coelicolor A3(2) is a model organism that has been used for more than five decades to study the genetic and biochemical basis for the production of bioactive metabolites. In 2002, the complete genome sequence of S. coelicolor was published. This greatly accelerated progress in understanding the biosynthesis of metabolites known or suspected to be produced by S. coelicolor and revealed that streptomycetes have far greater potential to produce bioactive natural products than suggested by classical bioassay-guided isolation studies. In this article, efforts to exploit the S. coelicolor genome sequence for the discovery of novel natural products and biosynthetic pathways are summarized.

Molecular beacons to identify gifted microbes for genome mining

“…[1][2][3][4] The genome mining concept stems from the seminal observations of the Hopwood and Ōmura groups that the genome sequences of Streptomyces coelicolor 5 and Streptomyces avermitilis 6 appeared to encode about 10-fold more potential secondary metabolites (SMs) than were known from the expressed secondary metabolomes. These predictions have been confirmed experimentally, 7,8 and generalized to actinomycetes and other bacterial taxa with large genomes. [9][10][11][12][13][14][15][16] NPs continue to be important sources of new and novel chemical scaffolds for drug discovery, 17,18 and actinomycetes, particularly Streptomyces species, continue to be the most productive sources.…”

Prospecting for new bacterial metabolites: a glossary of approaches for inducing, activating and upregulating the biosynthesis of bacterial cryptic or silent natural products

“…In Bacterial co-culturing has enabled the production and discovery of a number of new biologically active compounds. In 2001, growth of an unidentified Gram-negative bacterium CNJ-328 with a marine derived fungus, belonging to the Pestalotia spp., yielded a new chlorinated benzophenone, pestalone (19). 43 In 2003, co-culture of marine microbes C-148 and CF-20 with Vibrio anguillarum resulted in the production of a number of diketopiperazine (20) natural products with antibiotic properties, four of which had not been previously identified in nature.…”

“…coelicolor A3(2)) was published in the 2002 13 and the availability of its complete annotated sequence allowed the prediction and characterization of pathways involved in the production of at least 17 chemically distinct classes of bioactive compounds as reviewed by Challis 19 . Completely assembled and annotated genome sequences for over 65 Streptomycetes and hundreds of bacterial species demonstrated that more than 50% are likely to have one or more gene cluster involved in the biosynthesis of polyketides or non-ribosomal peptides.…”

Divalent Transition‐Metal‐Ion Stress Induces Prodigiosin Biosynthesis in Streptomyces coelicolor M145: Formation of Coeligiosins

“…[2,7] Clearly, the maintenance of secondary metabolite gene clusters and their formation is costly for the producing strains.…”

“…[5] With the genome sequencing of many Actinomyces such as the model Streptomycete Streptomyces coelicolor A3(2), [6] it became evident that these antibiotic producers comprise a lot more secondary metabolite gene clusters than secondary metabolites that have been identified from them. [2,7] Clearly, the maintenance of secondary metabolite gene clusters and their formation is costly for the producing strains. [8] In contrast to laboratory cultivation under optimized growth conditions, in their natural environment microorganisms have to cope with biotic and abiotic stress factors, for example, competition for space and nutrients.…”