Waschulin, V. | Search bioRxiv

bioRxiv2021

N-acetyl-cysteinylated streptophenazines fromStreptomyces

Here, we describe two N-acetyl-cysteinylated streptophenazines (1 and 2) produced by soil-derived Streptomyces sp. ID63040 and identified through a metabolomic approach. These metabolites attracted our interest due to their low occurrence frequency in a large library of fermentation broth extracts and their consistent presence in biological replicates of the producer strain. The compounds were found to possess broad-spectrum antibacterial activity while exhibiting low cytotoxicity. The biosynthetic gene cluster from Streptomyces sp. ID63040 was found to be highly similar to the streptophenazine reference cluster in the MIBiG database, which originates from the marine Streptomyces sp. CNB-091. Compounds 1 and 2 were the main streptophenazine products from Streptomyces sp. ID63040 at all cultivation times, but were not detected in Streptomyces sp. CNB-091. The lack of obvious candidates for cysteinylation in the Streptomyces sp. ID63040 biosynthetic gene cluster suggests that the N-acetyl-cysteine moiety derives from cellular functions, most likely from mycothiol. Overall, our data represent an interesting example on how to leverage metabolomics for the discovery of new natural products and point out to the often-neglected contribution of house-keeping cellular functions to natural product diversification. Graphical abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

microbiology↗

bioRxiv2020

Metabolic potential of uncultured Antarctic soil bacteria revealed through long-read metagenomic sequencing

The growing problem of antibiotic resistance has led to the exploration of uncultured bacteria as potential sources of new antimicrobials. PCR amplicon analyses and short-read sequencing studies of samples from different environments have reported evidence of high biosynthetic gene cluster (BGC) diversity in metagenomes. However, few complete BGCs from uncultivated bacteria have been recovered, making assessment of BGC diversity difficult. Here, long-read sequencing and genome mining were used to recover >1400 mostly complete BGCs that demonstrate the rich diversity of BGCs from uncultivated lineages present in soil from Mars Oasis, Antarctica. The phyla Acidobacteriota, Verrucomicrobiota and Gemmatimonadota, but also the actinobacterial classes Acidimicrobiia, Thermoleophilia, and the gammaproteobacterial order UBA7966, were found to encode a large number of highly divergent BGCs. Our findings underline the biosynthetic potential of underexplored phyla as well as unexplored lineages within seemingly well-studied producer phyla. They also showcase long-read metagenomic sequencing as a promising way to access the untapped reservoir of specialised metabolites of the uncultured majority of microbes.

microbiology↗