Abstract
Microbial natural products are compounds with unique chemical structures and diverse biological activities. Cyanobacteria commonly possess a wide range of biosynthetic gene clusters (BGCs) to produce natural products. Although natural product BGCs have been found in almost all cyanobacterial genomes, little attention has been given in cyanobacterial research to the partitioning of these biosynthetic pathways in chromosomes and plasmids. Cyanobacterial plasmids are believed to disperse several natural product BGCs, such as toxins, by plasmids through horizontal gene transfer. Therefore, plasmids may confer the ability to produce toxins and may play a role in the evolution of diverse natural product BGCs from cyanobacteria. Here, we performed an analysis of the distribution of natural product BGCs in 185 genomes and mapped the presence of genes involved in the conjugation in plasmids. The 185 analyzed genomes revealed 1817 natural products BGCs. Individual genomes contained 1–42 biosynthetic pathways (mean 8), 95% of which were present in chromosomes and the remaining 5% in plasmids. Of the 424 analyzed cyanobacterial plasmids, 12% contained homologs of genes involved in conjugation and natural product biosynthetic pathways. Among the biosynthetic pathways in plasmids, manual curation identified those to produce aeruginosin, anabaenopeptin, ambiguine, cryptophycin, hassallidin, geosmin, and microcystin. These compounds are known toxins, protease inhibitors, odorous compounds, antimicrobials, and antitumorals. The present study provides in silico evidence using genome mining that plasmids may be involved in the distribution of natural product BGCs in cyanobacteria. Consequently, cyanobacterial plasmids have importance in the context of biotechnology, water management, and public health risk assessment. Future research should explore in vivo conjugation and the end products of natural product BGCs in plasmids via chemical analyses.
Highlights
Microbial natural products originate from secondary metabolism and exhibit a wide range of chemical structures and biological activities (Woodruff, 1980)
Following the latest proposed system of cyanobacteria, 39% of the analyzed genomes belong to the order Synechococcales, followed by Nostocales (31% of genomes; largely represented by Nostoc and Calothrix) (Figure 1)
Our results indicated that 15 possibly conjugative plasmids harbored a total of 18 natural product biosynthetic gene clusters (BGCs) and 4 other mobilizable plasmids with 1 natural product BGC each
Summary
Microbial natural products originate from secondary metabolism and exhibit a wide range of chemical structures and biological activities (Woodruff, 1980). These metabolites can act as antibiotics, anticancer agents, antivirals, and toxins and can be used as enzyme inhibitors, polymers, or surfactants (Demain, 2014). The enzymes involved in the biosynthesis of natural products are commonly encoded in biosynthetic gene clusters (BGCs) located in contiguous stretches of DNA (Stone and Williams, 1992; Osbourn, 2010; Jensen, 2016). Genome mining, which uses bioinformatics techniques to identify genes encoding enzymes possibly involved in natural products biosynthesis, has led to the discovery of novel compounds (Corre and Challis, 2009; Zerikly and Challis, 2009; Bachmann et al, 2014). Cyanobacteria are among several phyla of bacteria that are commonly explored using these techniques (Micallef et al, 2015)
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