There is a real consensus that new antibiotics are urgently needed and are the best chance for combating antibiotic resistance. The phylum Actinobacteria is one of the main producers of new antibiotics, with a recent paradigm shift whereby rare actinomycetes have been increasingly targeted as a source of new secondary metabolites for the discovery of new antibiotics. However, this review shows that the genus Streptomyces is still the largest current producer of new and innovative secondary metabolites. Between January 2015 and December 2020, a significantly high number of novel Streptomyces spp. have been isolated from different environments, including extreme environments, symbionts, terrestrial soils, sediments and also from marine environments, mainly from marine invertebrates and marine sediments. This review highlights 135 new species of Streptomyces during this 6-year period with 108 new species of Streptomyces from the terrestrial environment and 27 new species from marine sources. A brief summary of the different pre-treatment methods used for the successful isolation of some of the new species of Streptomyces is also discussed, as well as the biological activities of the isolated secondary metabolites. A total of 279 new secondary metabolites have been recorded from 121 species of Streptomyces which exhibit diverse biological activity. The greatest number of new secondary metabolites originated from the terrestrial-sourced Streptomyces spp.

Lichens, which are defined by a symbiosis between a mycobiont (fungal partner) and a photobiont (photoautotrophic partner), are in fact complex assemblages of microorganisms that constitute a largely untapped source of bioactive secondary metabolites.

Salutary lessons from recent progress in re-engineering non-ribosomal peptide synthetase assembly lines, emphasizing effective strategies and key protein–protein interactions.

Mycale hentscheli is a marine sponge that is rich in bioactive small molecules. Here, we use direct metagenomic sequencing to elucidate highly complete and contiguous genomes for the major symbiotic bacteria of this sponge. We identify complete biosynthetic pathways for the three potent cytotoxic polyketides which have previously been isolated from M. hentscheli . Remarkably, and in contrast to previous studies of marine sponges, we attribute each of these metabolites to a different producing microbe. We also find that the microbiome of M. hentscheli is stably maintained among individuals, even over long periods of time. Collectively, our data suggest a cooperative mode of defensive symbiosis in which multiple symbiotic bacterial species cooperatively contribute to the defensive chemical arsenal of the holobiont.

Bacterial natural products have been a rich source of bioactive compounds for drug development, and advances in DNA sequencing, informatics and molecular biology have opened new avenues for their discovery. Here, we describe the isolation of an aureolic acid biosynthetic gene cluster from a metagenome library derived from a New Zealand soil sample. Heterologous expression of this pathway in Streptomyces albus resulted in the production and isolation of two new aureolic acid compounds, one of which (metathramycin, 6) possesses potent bioactivity against a human colon carcinoma cell line (HCT-116, IC₅₀ = 14.6 nM). As metathramycin was a minor constituent of the fermentation extract, its discovery relied on a combination of approaches including bioactivity guided fractionation, MS/MS characterisation and pathway engineering. This study not only demonstrates the presence of previously uncharacterised aureolic acids in the environment, but also the value of an integrated natural product discovery approach which may be generally applicable to low abundance bioactive metabolites.