Genome mining unveils widespread natural product biosynthetic capacity in human oral microbe Streptococcus mutans.

Liwei Liu,Tingting Hao,Zhoujie Xie,Geoff P Horsman,Yihua Chen

doi:10.1038/srep37479

Abstract

Streptococcus mutans is a major pathogen causing human dental caries. As a Gram-positive bacterium with a small genome (about 2 Mb) it is considered a poor source of natural products. Due to a recent explosion in genomic data available for S. mutans strains, we were motivated to explore the natural product production potential of this organism. Bioinformatic characterization of 169 publically available genomes of S. mutans from human dental caries revealed a surprisingly rich source of natural product biosynthetic gene clusters. Anti-SMASH analysis identified one nonribosomal peptide synthetase (NRPS) gene cluster, seven polyketide synthase (PKS) gene clusters and 136 hybrid PKS/NRPS gene clusters. In addition, 211 ribosomally synthesized and post-translationally modified peptides (RiPPs) clusters and 615 bacteriocin precursors were identified by a combined analysis using BAGEL and anti-SMASH. S. mutans harbors a rich and diverse natural product genetic capacity, which underscores the importance of probing the human microbiome and revisiting species that have traditionally been overlooked as “poor” sources of natural products.

Highlights

Streptococcus mutans is a major pathogen causing human dental caries
A total of 169 S. mutans genomes were analyzed with anti-SMASH and BAGEL, which identified 355 natural product gene clusters distributed among 138 S. mutans strains (Supplementary Tables SI, SII and SIII)
We have identified 355 natural product gene clusters from the genomes of 169 strains of the human oral microbe S. mutans, and 39% of these strains contained more than 2 clusters

Summary

Introduction

Streptococcus mutans is a major pathogen causing human dental caries. As a Gram-positive bacterium with a small genome (about 2 Mb) it is considered a poor source of natural products. Bioinformatic characterization of 169 publically available genomes of S. mutans from human dental caries revealed a surprisingly rich source of natural product biosynthetic gene clusters. The last three decades have witnessed tremendous progress in elucidating the biosynthetic mechanisms of varied microbial natural products including compounds synthesized by polyketide synthases (PKSs), nonribosomal peptide synthetases (NRPSs), and the ribosomally synthesized and post-translationally modified peptides (RiPPs). This genes-to-molecules foundational knowledge has enabled the identification of cryptic natural product gene clusters from microbial genomes and facilitated genomics guided discovery of novel natural products. A number of bacteriocins with diverse structures and bioactivities are generated by the action of various modification enzymes such as Ser/Thr dehydratases, methyltransferases, and macrocylases[9,10,11,12]

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