Renewed interests in the discovery of bioactive actinomycete metabolites driven by emerging technologies

Abstract

Actinomycetes are prolific sources of bioactive molecules. Traditional workflows including bacterial isolation, fermentation, metabolite identification, and structure elucidation have resulted in high rates of natural product rediscovery in recent years. Recent advancements in multi-omics techniques have uncovered cryptic gene clusters within the genomes of actinomycetes, potentially introducing vast resources for the investigation of bioactive molecules. While developments in culture techniques have allowed for the fermentation of difficult-to-culture actinomycetes, high throughput metabolite screening has offered plenary tools to accelerate hits discovery. A variety of new bioactive molecules have been isolated from actinomycetes of unique environmental origins, such as endophytic and symbiotic actinomycetes. Synthetic biology and genome mining have also emerged as new frontiers for the discovery of bioactive molecules. This review covers the highlights of recent developments in actinomycete-derived natural product drug discovery.

Exploring Micromonospora as Phocoenamicins Producers

“…These sources include forest organic soil, either dry or humid, rhizosphere soil from various plants, rice cultivations, soil in swamp ecosystems, marine sediments and finally a strain isolated from a marine invertebrate. This demonstrates that the production of phocoenamicins is not attributed to the unique environmental conditions, as previously believed [18,19]. Regarding their geographical origin, they were widely distributed worldwide, covering almost all continents.…”

Polyene Carboxylic Acids from a Streptomyces sp. Isolated from Tibet Soil

“…Actinobacteria have robust biosynthetic potential to produce bioactive compounds with broad structural diversity and commercial importance [ 4 , 5 ]. However, due to the frequent genetic exchange between species, the probability of the repeated discovery of known metabolites is increasing, and the difficulty of discovering new compounds is gradually increasing [ 6 , 7 , 8 , 9 ]. In order to increase the possibility of discovering new compounds, more and more researchers focus on actinomycetes in special environments.…”

Antibiotics from Insect-Associated Actinobacteria

“…Low-molecular compounds mediate insect interactions at various levels, from the individual level, where hormones control development and reproduction, to the interspecies level, where specific metabolites act as defense agents against predators [ 9 , 10 , 11 , 12 ]. Unsurprisingly, actinomycetes—one of the most fruitful producers of diverse secondary metabolites [ 13 , 14 , 15 ]—can interact with insects by biosynthesis of small molecules.…”