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Global Map of Specialized Metabolites Encoded in Prokaryotic Plasmids - PubMed

  • ️Sun Jan 01 2023

Global Map of Specialized Metabolites Encoded in Prokaryotic Plasmids

Zaki Saati-Santamaría. Microbiol Spectr. 2023.

Abstract

Plasmids are the main mobile elements responsible for horizontal gene transfer (HGT) in microorganisms. These replicons extend the metabolic spectrum of their host cells by carrying functional genes. However, it is still unknown to what extent plasmids carry biosynthetic gene clusters (BGCs) related to the production of secondary or specialized metabolites (SMs). Here, we analyzed 9,183 microbial plasmids to unveil their potential to produce SMs, finding a large diversity of cryptic BGCs in a few varieties of prokaryotic host taxa. Some of these plasmids harbored 15 or more BGCs, and many others were exclusively dedicated to mobilizing BGCs. We found an occurrence pattern of BGCs within groups of homologous plasmids shared by a common taxon, mainly in host-associated microbes (e.g., Rhizobiales, Enterobacteriaceae members). Our results add to the knowledge of the ecological functions and potential industrial uses of plasmids and shed light on the dynamics and evolution of SMs in prokaryotes. IMPORTANCE Plasmids are mobile DNA elements that can be shared among microbial cells, and they are useful for bringing to fruition some microbial ecological traits. However, it is not known to what extent plasmids harbor genes related to the production of specialized/secondary metabolites (SMs). In microbes, these metabolites are frequently useful for defense purposes, signaling, etc. In addition, these molecules usually have biotechnological and clinical applications. Here, we analyzed the content, dynamics, and evolution of genes related to the production of SMs in >9,000 microbial plasmids. Our results confirm that some plasmids act as a reservoir of SMs. We also found that some families of biosynthetic gene clusters are exclusively present in some groups of plasmids shared among closely related microbes. Host-associated bacteria (e.g., plant and human microbes) harbor the majority of specialized metabolites encoded in plasmids. These results provide new knowledge about microbial ecological traits and might enable the discovery of novel metabolites.

Keywords: megaplasmids; microbial ecology; plasmids; secondary metabolism.

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Conflict of interest statement

The author declares no conflict of interest.

Figures

FIG 1
FIG 1

Density of BGCs within plasmids from diverse host cell taxa. (a) Representation of the number of BGCs harbored within prokaryotic plasmids (y axis) and the plasmid size (x axis). Some plasmids with a high BGC content and diversity are highlighted (GenBank accession numbers are shown in parentheses). (b) Density of BGCs in plasmids from different phyla. Phyla with no BGC-carrying plasmids are not displayed.

FIG 2
FIG 2

BGC content and coverage within prokaryotic plasmids. The length of some plasmids is as long as the sum of the lengths of their BGCs, while many other plasmids dedicate most of their size for other purposes (a). These results are not an effect of the BGC type or size (b). In addition, the occurrence of diverse BGC types is not related to plasmid size (c). Note: the BGC region sizes might be overestimated due to in silico prediction biases.

FIG 3
FIG 3

Diversity of BGCs within plasmids. (a) Sequence similarity network (SSN) built based on BGC distances. Each dot represents a BGC, colored according to the BGC type, and those sharing high similarity are connected with gray lines. Gene cluster families (GCFs) and/or GCF clades are grouped within independent clusters. The network includes previously described BGCs (from the MIBiG database) closely related to those found in the plasmid data set, indicated with a black, dotted circle. The MIBiG-BGCs found in the largest clusters of BGCs are labeled with their encoded product. GCFs present exclusively in plasmids from certain host taxa (species, genus, family, or order) are accompanied by the taxon name, including those solely found in PTUs. Red text specify certain types of large BGC clusters classified as RiPPs or others. (b) Representation of the total number of BGCs of each type found in plasmids, including singletons. (c) Number of BGCs of each type in the plasmids of each of the host cell orders in this study.

FIG 4
FIG 4

Biosynthetic potential of Ralstonia solanacearum PTU-Bur3 plasmids (shown with their GenBank accession numbers). The number of BGCs from each type in Ralstonia solanacearum PTU-Bur3 plasmids is shown, and the plasmids are ordered by their patterns of occurrence and abundance.

FIG 5
FIG 5

Desferrioxamine gene cluster family. The phylogeny of the GCF was built based on desferrioxamine clusters found in S. cattleya plasmids (blue text), including several homologs described in chromosomal units (black text).

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