Genome Analysis of the Fruiting Body-Forming Myxobacterium Chondromyces crocatus Reveals High Potential for Natural Product Biosynthesis

Abstract

Here, we report the complete genome sequence of the type strain of the myxobacterial genus Chondromyces, Chondromyces crocatus Cm c5. It presents one of the largest prokaryotic genomes featuring a single circular chromosome and no plasmids. Analysis revealed an enlarged set of tRNA genes, along with reduced pressure on preferred codon usage compared to that of other bacterial genomes. The large coding capacity and the plethora of encoded secondary metabolite biosynthetic gene clusters are in line with the capability of Cm c5 to produce an arsenal of antibacterial, antifungal, and cytotoxic compounds. Known pathways of the ajudazol, chondramide, chondrochloren, crocacin, crocapeptin, and thuggacin compound families are complemented by many more natural compound biosynthetic gene clusters in the chromosome. Whole-genome comparison of the fruiting-bodyforming type strain (Cm c5, DSM 14714) to an accustomed laboratory strain which has lost this ability (nonfruiting phenotype, Cm c5 fr؊) revealed genetic changes in three loci. In addition to the low synteny found with the closest sequenced representative of the same family, Sorangium cellulosum, extensive genetic information duplication and broad application of eukaryotic-type signal transduction systems are hallmarks of this 11.3-Mbp prokaryotic genome. Myxobacteria represent a branch of Deltaproteobacteria with exceptionally large and GC-rich genomes. Usually isolated from soil, these bacteria are best known for a complex development cycle and as prolific producers of secondary metabolites exhibiting a broad variety of biological activities (1). The chemical diversity of the produced compounds has motivated scientists to study more myxobacterial strains, with an emphasis on phylogenetic variety (2, 3, 4). Several genomes of secondary metaboliteproducing myxobacteria have been completely sequenced (5, 6). They exhibit genome sizes ranging from 9.2 to 14.7 Mbp, including the currently largest known bacterial genome of Sorangium cellulosum So0157-2 (7). The genomic diversity of myxobacteria is vast, and even strains of the same species may undergo genome reduction or expansion at an order of millions of base pairs (6, 7). Such diversity coincides with deviations in the genomic content of secondary metabolite biosynthetic gene clusters of known genomes, ranging from a prediction of 19 such clusters in Sandaracinus amylolyticus DSM 53668 to an estimated 38 clusters in Sorangium cellulosum So0157-2. Therefore, to better understand the biosynthetic capabilities of the myxobacteria and the relative frequency of secondary metabolites encoded in their genomes, more representatives are required to be sequenced. We here report our analysis of the genome sequence of Chondromyces crocatus Cm c5, the first representative of the genus Chondromyces belonging to the family of the Sorangiineae. MATERIALS AND METHODSGenome sequencing. The genome sequence of Chondromyces crocatus Cm c5 was determined through a combination of next-and thirdgeneration technologies available at the Helmho...

Structure and Biosynthesis of Crocagins: Polycyclic Posttranslationally Modified Ribosomal Peptides from Chondromyces crocatus

“…[1] Dozens of novel compound classes have been isolated from myxobacteria, including many that appear to be exclusively produced by them. [9] Acomputational estimation of the encoded secondary metabolite potential using antiSMASH [10] revealed an outstanding 19 gene clusters with nonribosomal peptide synthetase (NRPS) or polyketide synthase (PKS) genes, [11] less than at hird of which have been correlated to secondary metabolites to date.I na ddition, several gene clusters encoding ribosomally synthesized and post-translationally modified peptides (RiPPs) belonging to the bacteriocin and lantipeptide families have been predicted. [4] Chondromyces crocatus Cm c5 is an exceptionally prolific myxobacterial producer of multiple bioactive natural product families,s uch as the chondramides, [5] ajudazols, [6] crocacins, [7] crocapeptins, [8] and thuggacins.…”

“…[2,3] Thef ull extent of their potential to form secondary metabolites has only emerged in recent years, since fully sequenced genomes and computational genome analysis tools have become available.P redictions based on genome sequence analysis indicate as econdary metabolite potential in myxobacteria that far exceeds the currently known compounds. [9] Acomputational estimation of the encoded secondary metabolite potential using antiSMASH [10] revealed an outstanding 19 gene clusters with nonribosomal peptide synthetase (NRPS) or polyketide synthase (PKS) genes, [11] less than at hird of which have been correlated to secondary metabolites to date.I na ddition, several gene clusters encoding ribosomally synthesized and post-translationally modified peptides (RiPPs) belonging to the bacteriocin and lantipeptide families have been predicted. [9] Acomputational estimation of the encoded secondary metabolite potential using antiSMASH [10] revealed an outstanding 19 gene clusters with nonribosomal peptide synthetase (NRPS) or polyketide synthase (PKS) genes, [11] less than at hird of which have been correlated to secondary metabolites to date.I na ddition, several gene clusters encoding ribosomally synthesized and post-translationally modified peptides (RiPPs) belonging to the bacteriocin and lantipeptide families have been predicted.…”

“…[4] Chondromyces crocatus Cm c5 is an exceptionally prolific myxobacterial producer of multiple bioactive natural product families,s uch as the chondramides, [5] ajudazols, [6] crocacins, [7] crocapeptins, [8] and thuggacins. [9] Acomputational estimation of the encoded secondary metabolite potential using antiSMASH [10] revealed an outstanding 19 gene clusters with nonribosomal peptide synthetase (NRPS) or polyketide synthase (PKS) genes, [11] less than at hird of which have been correlated to secondary metabolites to date.I na ddition, several gene clusters encoding ribosomally synthesized and post-translationally modified peptides (RiPPs) belonging to the bacteriocin and lantipeptide families have been predicted. RiPPs are ahighly diverse group of natural products with abroad spectrum of biological functions.…”

Complete Genome Sequence of the Fruiting Myxobacterium Myxococcus macrosporus Strain DSM 14697, Generated by PacBio Sequencing

“…Only 20 genomes of the Myxococcales have been completely sequenced ( 5 , 8 – 24 ). In addition, 36 Myxococcales draft genomes are available ( 25 – 32 ).…”

Chemische Struktur und Biosynthese der Crocagine, polycyclischer Peptide ribosomalen Ursprungs aus Chondromyces crocatus

“…B. der Chondramide, Ajudazole, Crocacine, Crocapeptine und Thuggacine . Eine rechnerbasierte Genomanalyse mit antiSMASH ergab 19 Gencluster mit nichtribosomalen Peptidsynthetase(NRPS)‐ oder Polyketidsynthase(PKS)‐Genen, wobei davon bis jetzt weniger als ein Drittel bekannten Naturstoffen zugeordnet ist. Darüber hinaus wurden mehrere Gencluster für ribosomal produzierte und posttranslational modifizierte Peptide (RiPPs) prognostiziert, die zu den Familien der Bacteriocine und Lantipeptide gehören.…”