Discovering the Hidden Secondary Metabolome of Myxococcus xanthus : a Study of Intraspecific Diversity

Abstract

As a monophyletic group, the myxobacteria are known to produce a broad spectrum of secondary metabolites. However, the degree of metabolic diversity that can be found within a single species remains unexplored. The model species Myxococcus xanthus produces several metabolites also present in other myxobacterial species, but only one compound unique to M. xanthus has been found to date. Here, we compare the metabolite profiles of 98 M. xanthus strains that originate from 78 locations worldwide and include 20 centimeter-scale isolates from one location. This screen reveals a strikingly high level of intraspecific diversity in the M. xanthus secondary metabolome. The identification of 37 nonubiquitous candidate compounds greatly exceeds the small number of secondary metabolites previously known to derive from this species. These results suggest that M. xanthus may be a promising source of future natural products and that thorough intraspecific screens of other species could reveal many new compounds of interest.Prokaryotes continue to provide important leads in the search for medically important bioactive natural products (1, 11). In particular, the myxobacteria have emerged as a promising source of natural products that exhibit highly diverse structures and biological activities (9). While most myxobacterial genera produce secondary metabolites, difficulties with cultivation and genetic manipulation hinder exploitation of the biosynthetic potential of many species. In contrast, the relatively fast growth and extensive genetic characterization of Myxococcus xanthus make the identification of natural products in this model species of particular interest.Myxococcus xanthus has been thoroughly investigated due to its amazing social behaviors, which include coordinated swarming over surfaces and a complex life cycle that culminates in the formation of multicellular fruiting bodies under starvation conditions (23). However, little attention has been paid to secondary metabolite production in this model species. M. xanthus strain DK1622 is the genotype most commonly studied with respect to social interactions and development. This strain has been found to produce several secondary metabolites, including the myxochromids (27), myxalamids (13), the antibiotic myxovirescin (8), and the siderophore myxochelin (15) (Fig. 1A). The molecular basis of synthesis for these compounds has been studied in some detail (25,26,30) and has been greatly facilitated by the availability of the DK1622 genome sequence (10). Very recently, a novel secondary metabolite class unique to M. xanthus, the DKxanthenes, was characterized and was shown to be essential for viable-spore formation (18). Additional reports of secondary metabolites from M. xanthus are limited to cittilin (20) and the antibiotics saframycin (12) and althiomycin (16).Most of these M. xanthus compounds are polyketides or nonribosomal peptides or hybrids thereof, and their biosynthesis is accomplished by large multienzyme complexes, the polyketide synthases (PKSs) or the nonri...

Endemic social diversity within natural kin groups of a cooperative bacterium

“…A high level of phenotypic and genetic diversity has been documented among cm-scale M. xanthus isolates (7,36,(42)(43)(44)(45), despite the fact that genetic diversity at this scale was found to be much lower than at only slightly larger sampling scales (8). For example, genetically similar centimeter-scale isolates were found to show extremely divergent competitive abilities during fruiting body development in forcibly mixed pairings (36).…”

Selection of KYC 3270, a Cellulolytic Myxobacteria of Sorangium cellulosum, against Several Phytopathogens and a Potential Biocontrol Agent against Gray Mold in Stored Fruit

“…In addition, the percentage of extracts that caused clear zones due to inhibited spore germination of three or four fungi was 15−44% for cellulolytic but only 0− 6% for bacteriolytic myxobacteria. Although most research on bioactivity has been conducted on bacteriolytic myxobacteria (Bull et al, 2002;Chung et al, 2008;Kim et al, 1998;Kim et al, 2003b;Krug et al, 2008;Kim and Yun, 2011), more cellulolytic myxobacteria should be studied because they have superior antifungal activity to bacteriolytic myxobacteria. Among the five tested phytopathogens, B. cinerea was the best controlled with 455 myxobacterial extracts.…”

“…(Ahn and Kim, 2002;Bull et al, 2002;Chung et al, 2008;Kim and Yun, 2011;Kim et al, 1998;Kim et al, 2003b;Krug et al, 2008), although the antifungal activity of S. cellulosum, a cellulolytic myxobacterium, against several phytopathogenic fungi has been examined in Germany (Reichenbach and Höfle, 1994). Soraphen and epothilone are two natural products of S. cellulosum, and soraphen in particular is an antifungal compound.…”

Biocontrol with Myxococcus sp. KYC 1126 Against Anthracnose in Hot Pepper

“…Myxobacteria are a rich source of bioactive secondary metabolites that are not found in other antagonists such as pseudomonads and Bacillus spp. and are being evaluated as a source of novel compounds (Bull et al, 2002;Dawid, 2000;Gaspari et al, 2005;Gerth et al, 2003;Krug et al, 2008;Reichenbach, 2001). In studies over more than 25 years, about 80 basic structures and 350 variants have been identified.…”

“…The bacteriolytic myxobacteria produce the agriculturally important antibiotic, pyrrolnitrin. The genera Myxococcus, Corallococcus, Cystobacter, Archangium, and Stigmatella are bacteriolytic myxobacteria and are rich sources of bioactive metabolites including aurachin, corallopyronin, crocacin, myxalamid, myxochelin, myxothiazol, myxovirescin, pyrrolnitrin, saframycin, and stigmatellin (Bartlett et al, 2002;Dawid, 2000;Kim et al, 2003;Krug et al, 2008;Reichenbach, 2001;Wang and Tao, 2009).…”