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Survey of Biosynthetic Gene Clusters from Sequenced Myxobacteria Reveals Unexplored Biosynthetic Potential.

ABSTRACT: Coinciding with the increase in sequenced bacteria, mining of bacterial genomes for biosynthetic gene clusters (BGCs) has become a critical component of natural product discovery. The order Myxococcales, a reputable source of biologically active secondary metabolites, spans three suborders which all include natural product producing representatives. Utilizing the BiG-SCAPE-CORASON platform to generate a sequence similarity network that contains 994 BGCs from 36 sequenced myxobacteria deposited in the antiSMASH database, a total of 843 BGCs with lower than 75% similarity scores to characterized clusters within the MIBiG database are presented. This survey provides the biosynthetic diversity of these BGCs and an assessment of the predicted chemical space yet to be discovered. Considering the mere snapshot of myxobacteria included in this analysis, these untapped BGCs exemplify the potential for natural product discovery from myxobacteria.

SUBMITTER: Gregory K

PROVIDER: S-EPMC6616573 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Survey of Biosynthetic Gene Clusters from Sequenced Myxobacteria Reveals Unexplored Biosynthetic Potential.

Gregory Katherine K Salvador Laura A LA Akbar Shukria S Adaikpoh Barbara I BI Stevens D Cole DC

Microorganisms 20190624 6

Coinciding with the increase in sequenced bacteria, mining of bacterial genomes for biosynthetic gene clusters (BGCs) has become a critical component of natural product discovery. The order Myxococcales, a reputable source of biologically active secondary metabolites, spans three suborders which all include natural product producing representatives. Utilizing the BiG-SCAPE-CORASON platform to generate a sequence similarity network that contains 994 BGCs from 36 sequenced myxobacteria deposited i ...[more]

PMID: 31238501

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Project description:Through screening of rhizobacteria, species that effectively suppress phytopathogens and/or promote plant growth are found. Genome sequencing is a crucial step in obtaining a complete characterization of microorganisms for biotechnological applications. This study aimed to sequence the genomes of four rhizobacteria that differ in their inhibition of four root pathogens and in their interaction with chili pepper roots to identify the species and analyze differences in the biosynthetic gene clusters (BGCs) for antibiotic metabolites and to determine possible phenotype-genotype correlations. Results from sequencing and genome alignment identified two bacteria as Paenibacillus polymyxa, one as Kocuria polaris, and one that was previously sequenced as Bacillus velezensis. Analysis with antiSMASH and PRISM tools showed that B. velezensis 2A-2B, the strain with the best performance of referred characteristics, had 13 BGCs, including those related to surfactin, fengycin, and macrolactin, not shared with the other bacteria, whereas P. polymyxa 2A-2A and 3A-25AI, with up to 31 BGCs, showed lower pathogen inhibition and plant hostility; K. polaris showed the least antifungal capacity. P. polymyxa and B. velezensis had the highest number of BGCs for nonribosomal peptides and polyketides. In conclusion, the 13 BGCs in the genome of B. velezensis 2A-2B that were not present in the other bacteria could explain its effective antifungal capacity and could also contribute to its friendly interaction with chili pepper roots. The high number of other BGCs for nonribosomal peptides and polyketide shared by the four bacteria contributed much less to phenotypic differences. IMPORTANCE To advance the characterization of a microorganism as a biocontrol agent against phytopathogens, it is highly recommended to analyze the potential of the profile of secondary metabolites as antibiotics that it produces to counteract pathogens. Some specific metabolites have positive impacts in plants. By analyzing sequenced genomes with bioinformatic tools, such as antiSMASH and PRISM, outstanding bacterial strains with high potential to inhibit phytopathogens and/or promote plant growth can be quickly selected to confirm and expand our knowledge of BGCs of great value in phytopathology.

Project description:Small molecules are the primary communication media of the microbial world. Recent bioinformatic studies, exploring the biosynthetic gene clusters (BGCs) which produce many small molecules, have highlighted the incredible biochemical potential of the signaling molecules encoded by the human microbiome. Thus far, most research efforts have focused on understanding the social language of the gut microbiome, leaving crucial signaling molecules produced by oral bacteria and their connection to health versus disease in need of investigation. In this study, a total of 4,915 BGCs were identified across 461 genomes representing a broad taxonomic diversity of oral bacteria. Sequence similarity networking provided a putative product class for more than 100 unclassified novel BGCs. The newly identified BGCs were cross-referenced against 254 metagenomes and metatranscriptomes derived from individuals either with good oral health or with dental caries or periodontitis. This analysis revealed 2,473 BGCs, which were differentially represented across the oral microbiomes associated with health versus disease. Coabundance network analysis identified numerous inverse correlations between BGCs and specific oral taxa. These correlations were present in healthy individuals but greatly reduced in individuals with dental caries, which may suggest a defect in colonization resistance. Finally, corroborating mass spectrometry identified several compounds with homology to products of the predicted BGC classes. Together, these findings greatly expand the number of known biosynthetic pathways present in the oral microbiome and provide an atlas for experimental characterization of these abundant, yet poorly understood, molecules and socio-chemical relationships, which impact the development of caries and periodontitis, two of the world's most common chronic diseases.IMPORTANCE The healthy oral microbiome is symbiotic with the human host, importantly providing colonization resistance against potential pathogens. Dental caries and periodontitis are two of the world's most common and costly chronic infectious diseases and are caused by a localized dysbiosis of the oral microbiome. Bacterially produced small molecules, often encoded by BGCs, are the primary communication media of bacterial communities and play a crucial, yet largely unknown, role in the transition from health to dysbiosis. This study provides a comprehensive mapping of the BGC repertoire of the human oral microbiome and identifies major differences in health compared to disease. Furthermore, BGC representation and expression is linked to the abundance of particular oral bacterial taxa in health versus dental caries and periodontitis. Overall, this study provides a significant insight into the chemical communication network of the healthy oral microbiome and how it devolves in the case of two prominent diseases.

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Survey of Biosynthetic Gene Clusters from Sequenced Myxobacteria Reveals Unexplored Biosynthetic Potential.

Publications

Survey of Biosynthetic Gene Clusters from Sequenced Myxobacteria Reveals Unexplored Biosynthetic Potential.

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