Myxobacterial Genomics and Post-Genomics: A Review of Genome Biology, Genome Sequences and Related ‘Omics Studies

Abstract

Myxobacteria are fascinating and complex microbes. They prey upon other members of the soil microbiome by secreting antimicrobial proteins and metabolites, and will undergo multicellular development if starved. The genome sequence of the model myxobacterium Myxococcus xanthus DK1622 was published in 2006 and 15 years later, 163 myxobacterial genome sequences have now been made public. This explosion in genomic data has enabled comparative genomics analyses to be performed across the taxon, providing important insights into myxobacterial gene conservation and evolution. The availability of myxobacterial genome sequences has allowed system-wide functional genomic investigations into entire classes of genes. It has also enabled post-genomic technologies to be applied to myxobacteria, including transcriptome analyses (microarrays and RNA-seq), proteome studies (gel-based and gel-free), investigations into protein–DNA interactions (ChIP-seq) and metabolism. Here, we review myxobacterial genome sequencing, and summarise the insights into myxobacterial biology that have emerged as a result. We also outline the application of functional genomics and post-genomic approaches in myxobacterial research, highlighting important findings to emerge from seminal studies. The review also provides a comprehensive guide to the genomic datasets available in mid-2021 for myxobacteria (including 24 genomes that we have sequenced and which are described here for the first time).

Constructing a Myxobacterial Natural Product Database to Facilitate NMR-Based Metabolomics Bioprospecting of Myxobacteria

“…Remarkably, a considerable portion (∼60%) is bioactive polyketides that are derived from modular NRPS–PKS hybrids, with one of the most prominent examples being epothilone. Notably, RiPPs (ribosomally synthesized and post-translationally modified peptides) gene clusters are quite widespread in myxobacteria, , but only four skeletons (cittilin, myxarylin, crocagin, fulvocin C,) match, indicating a vast chemical space yet to be discovered. While various backbones orchestrated by type II PKS are commonplace in Gram-positive actinomycetes, there is only one example, namely, pyxidicyclines from Gram-negative myxobacteria …”

“…Microbial natural products (NPs) are a bountiful source for new drug development, and the discovery of novel chemical scaffolds has been a consistent goal of NP research. Myxobacteria are a group of Gram-negative bacteria ubiquitous on Earth and featured a sophisticated social life cycle. , According to the latest taxonomy, myxobacteria are reclassified as a new phylum Myxococcota , which has received considerable attention in recent years mostly because they have been proven to produce a large repertoire of secondary metabolites with superlative architectural complexity and outstanding biological potency. , This branch of life has recently been added to the list of “gifted” taxa for genome mining and natural product discovery, standing with filamentous actinomycetes , Bacillus , and Pseudomonas . , However, myxobacteria are still a clique of far underexplored microorganisms because large-scale (meta)­genome mining has culminated in voluminous untapped biosynthetic gene clusters (BGCs) in myxobacteria, − and even in the best-studied model Myxococcus xanthus DK1622, only a small fraction of BGCs have metabolite match. , Therefore, there is an enticing prospect for myxobacteria to deliver many more drug leads, and it is critical to developing effective pipelines for the excavation of this tremendous treasure trove.…”

The RNA cargo of Myxococcus outer membrane vesicles

“…24,27 These shared features of myxobacterial OMV transcriptomes and OMV proteomes in turn mirror the myxobacterial pan-genome, which comprises a relatively small core genome, with a large and highly variable accessory genome. 28,29 Enrichment of specific molecular species in OMVs compared to their relative abundance in the cell is indicative of cargo selection and usually assumed to be adaptive. A small number of core OMV transcripts were found to be enriched, but enrichment of those transcripts was not typically conserved, and many OMV transcripts were not enriched at all.…”

In Silico and In Vitro Analyses Reveal Promising Antimicrobial Peptides from Myxobacteria

“…M. macrosporus HW-1, previously known as Myxococcus fulvus HW-1, was recently classified based on its genomic features [ 34 ]. The genome encoded 72 putative AMP sequences with K. pneumoniae (37%) being the pathogen most AMPs were predicted to be active against and S. aureus (3%) with least activity.…”