40k erebus
Thus, the exploration of new microbial resources comparable to actinomycetes is extremely important.
Nevertheless, it is of high risk to focus the discovery of novel natural products on only a single phylum as this source could become exhausted. Furthermore, the application of in silico biosynthetic predictions from genome mining data and novel developed heterologous expression technologies confirm the phylum Actinobacteria as a continuing source of novel antibiotics ( Bérdy, 2012 Genilloud, 2017). Given that, isolation and screening of rare actinomycetes and marine-derived actinomycetes have become popular. In contrast, the ratio has decreased to 25% in the 2000s to 2010s, with the silencing of gene clusters encoding biosynthetic enzymes required for natural products under laboratory conditions further hampering the discovery of novel antibiotics via the traditional bacterial fermentation method ( Rutledge and Challis, 2015). Traditionally, Actinobacteria, particularly the genus Streptomyces, has served as the major producer of antimicrobial natural products, contributing 62% of the microbe-derived antibiotics from the 1950s to 1970s ( Bérdy, 2012). However, misuse and overuse of antibiotics has led to the accelerating development of antibiotic resistance in pathogens, which has become a major threat to modern health care and the natural environment ( Pal et al., 2016 Jiang et al., 2017). The discovery and clinical application of antimicrobial drugs have greatly improved our well-being with regard to microbial infection over the past several decades ( Demain and Sanchez, 2009). Based on these findings, we propose the ancient, ubiquitous, and spore-forming Ktedonobacteria as a versatile and promising microbial resource for natural product discovery. Furthermore, screening of bioactive compounds from representative Ktedonobacteria strains resulted in the identification of broad antimicrobial activities against both Gram-positive and Gram-negative tested bacterial strains. Our investigation of domain composition and organization of the non-ribosomal peptide synthetase and polyketide synthase BGCs further supports the concept that class Ktedonobacteria may produce compounds structurally different from known natural products. Furthermore, a total of 104 antiSMASH-predicted putative biosynthetic gene clusters (BGCs) for secondary metabolites with high novelty and diversity were identified in nine Ktedonobacteria genomes. In this study, we observed the existence of a putative “megaplasmid,” multiple copies of ribosomal RNA operons, and high ratio of hypothetical proteins with unknown functions in the class Ktedonobacteria. These characteristics indicate Ktedonobacteria as a potential active producer of bioactive compounds. Ktedonobacteria, a class of deeply branched bacterial lineage in the ancient phylum Chloroflexi, are ubiquitous in terrestrial environments and characterized by their large genome size and complex life cycle. The prevalence of antibiotic resistance and the decrease in novel antibiotic discovery in recent years necessitates the identification of potentially novel microbial resources to produce natural products.