Biology subjects

Mevers, E.

Publications and source records attributed to Mevers, E..

5 recordsLinked to original sources

bioRxiv2025

Fine-Grained Structural Classification of Biosynthetic Gene Cluster-Encoded Products

Biosynthetic gene clusters (BGCs) are responsible the biosynthesis of many natural products, including a multitude of effective therapeutics and their precursors. Advances in genomic data collection as well as computational techniques have made it possible to identify BGCs at scale. However, accurately determining the types of BGC-encoded products from genomic content remains elusive. Here, we introduce BGCat (BGC annotation tool), a machine learning method for fine-grained structural classification of BGC-encoded products, leveraging the NPClassifier natural product nomenclature. Our method leverages a pre-trained protein language model for creating meaningful gene representations and a deep neural network for class label prediction. We show the method outperforms state-of-the-art approaches in coarse-grained product classification and is effective for detailed classification. We implement a clustering-based augmentation strategy for BGC-product relationships, addressing a crucial gap in the available datasets. We then introduce the concept of product class profiles (PCPs) of gene cluster families (GCFs), associating each GCF with a probabilisitc distribution of product types and offering a new perspective on GCF functions. Lastly, we use BGCat to provide new product class labels for over 100k BGCs in antiSMASH DB that presently have minimal information about their products.

bioinformatics↗

bioRxiv2024

The Microbiota of Moon Snail Egg Collars is Shaped by Host-Specific Factors

Moon Snails lay eggs using a mixture of mucus and sediment to form an egg mass commonly referred to as an egg collar. These collars do not appear to experience micro-biofouling or predation and this observation led us to hypothesize that the egg collars possess a chemically-rich microbiota that protect the egg collars from pathogens. Herein, we sought to gain an understanding of the bacterial composition of the egg collars by amplifying and sequencing the 16S rRNA gene from egg collar and sediment samples collected at four distinct geographical regions in SW Florida. Relative abundance and non-metric multidimensional scaling plots revealed distinct differences in the bacterial composition between the egg collar and sediment samples. In addition, the egg collars had a lower -diversity than the sediment, with specific genera being significantly enriched in the egg collars. Analysis of microorganisms consistent across two seasons suggests that Flavobacteriaceae make up a large portion of the core microbiota (36 - 58% of 16S sequences). We also investigated the natural product potential of the egg collar microbiota by sequencing a core biosynthetic gene, the adenylation domains (AD), within the gene clusters of non-ribosomal peptide synthetase (NRPS). AD sequences matched multiple modules within known bioactive NRPs biosynthetic gene clusters, suggesting production is possible within the egg collar system and lays the foundation for future studies into the chemical and ecological role of this microbiota. IMPORTANCEAnimals commonly partner with microorganisms to accomplish essential tasks, including chemically defending the animal host from predation and/or infections. Understanding animal-microbe partnerships and the molecules used by the microbe to defend the animals from pathogens or predation have the potential to lead to new pharmaceutical agents. However, very few of these systems have been investigated. A particularly interesting system are nutrient rich marine egg collars, which often lack visible protections, and are hypothesized to harbor beneficial microbes that protect the eggs. In this study, we gained an understanding of the bacterial strains that form the core microbiota of Moon Snail egg collars and gained a preliminary understanding of their natural product potential. This work lays the foundation for future work to understand the ecological role of the core microbiome and to study the molecules involved in chemically defending the Moon Snail eggs.

bioinformatics↗

bioRxiv2023

Lactiplantibacillus plantarum uses ecologically relevant, exogenous quinones for extracellular electron transfer

Extracellular electron transfer (EET) is a metabolic process that frequently uses quinones to couple intracellular redox reactions with extracellular electron acceptors. The physiological relevance of this metabolism for microorganisms that are capable of EET, but unable to synthesize their own quinones, remains to be determined. To address this question, we investigated quinone utilization by Lactiplantibacillus plantarum, a microorganism required for food fermentations, performs EET, and is also a quinone auxotroph. L. plantarum selectively used 1,4-dihydroxy-2-naphthoic acid (DHNA), 2-amino-3-carboxy-1,4-naphthoquinone (ACNQ), 1,4-naphthoquinone, and menadione for EET reduction of insoluble iron (ferrihydrite). However, those quinones used for EET also inhibited L. plantarum growth in non-aerated conditions. Transcriptomic analysis showed that DHNA induced oxidative stress in L. plantarum and this was alleviated by the inclusion of an electron acceptor, soluble ferric ammonium citrate (FeAC), in the laboratory culture medium. The presence of DHNA and FeAC during growth also induced L. plantarum EET metabolism, although activity was still dependent on the presence of exogenous electron shuttles. To determine whether quinone-producing bacteria frequently found together with L. plantarum in food fermentations could be a source of those electron shuttles, L. plantarum EET was measured after incubation with Lactococcus lactis and Leuconostoc mesenteroides. Quinone-producing L. lactis, but not a quinone-deficient L. lactis {Delta}menC mutant, increased L. plantarum ferrihydrite reduction and medium acidification through an EET-dependent mechanism. L. plantarum EET was also stimulated by L. mesenteroides, and this resulted in greater environmental acidification and transient increases in L. plantarum growth. Overall, our findings revealed that L. plantarum overcomes the toxic effects of exogenous quinones to use those compounds, including those made by related bacteria, for EET-conferred, ecological advantages during the early stages of food fermentations.

microbiology↗

bioRxiv2020

Bacterially produced small molecules stimulate diatom growth

Diatoms are photosynthetic microalgae that fix a significant fraction of the worlds carbon. Because of their photosynthetic efficiency and high-lipid content, diatoms are priority candidates for biofuel production. Here, we report that sporulating Bacillus thuringiensis when in co-culture with a marine diatom Phaeodactylum tricornutum significantly increases the diatom cell count. Bioassay-guided purification led to the identification of two diketopiperazines (DKPs) that both stimulate P. tricornutum growth and increase its lipid content. RNA-seq analysis revealed upregulation of a small set of P. tricornutum genes involved in iron starvation response and nutrient recycling when DKP was added to the diatom culture. This work demonstrates that two DKPs produced by a bacterium could positively impact P. tricornutum growth and lipid content, offering new approaches to enhance P. tricornutum-based biofuel production. As increasing numbers of DKPs are isolated from marine microbes, the work gives potential clues to bacterially produced growth factors for marine microalgae. One sentence summaryTwo diketopiperazines (DKPs) produced by sporulating bacterium Bacillus thuringiensis stimulate diatom P. tricornutum growth and increase diatom lipid content.

plant biology↗

bioRxiv2018

Amycomicin: a potent and specific antibiotic discovered with a targeted interaction screen

The rapid emergence of antibiotic-resistant pathogenic bacteria has accelerated the search for new antibiotics. Many clinically used antibacterials were discovered through culturing a single microbial species under nutrient-rich conditions, but in the environment, bacteria constantly encounter poor nutrient conditions and interact with neighboring microbial species. In an effort to recapitulate this environment we generated a nine-strain Actinomycete community and used 16S rDNA sequencing to deconvolute the stochastic production of antimicrobial activity that was not observed from any of the axenic cultures. We subsequently simplified the community to just two strains and identified Amycolatopsis sp. AA4 as the producing strain and Streptomyces coelicolor M145 as an inducing strain. Bioassay-guided isolation identified amycomicin, a highly modified fatty acid containing an epoxide isonitrile warhead as a potent and specific inhibitor of Staphylococcus aureus. Amycomicin targets an essential enzyme in fatty acid biosynthesis (FabH) and reduces S. aureus infection in a mouse skin infection model. The discovery of amycomicin demonstrates the utility of screening complex communities against specific targets to discover small-molecule antibiotics.\n\nSignificanceBacteria, especially actinomycetes, produce the majority of our clinically useful small-molecule antibiotics. Genomic analyses of antibiotic-producing strains indicate that earlier discovery efforts found only a fraction of the likely antibiotic candidates. In an effort to uncover these previously missed candidates we developed an approach that utilizes the ability of microbial communities to produce antibiotics that are not produced by any single member in isolation. Successful communities were established and deconvoluted to identify both producers and inducers of antibiotic activity. One inducer-producer pair made amycomicin, a potent and specific antibiotic against Staphylococcus aureus, an important human pathogen. Amycomicin targets fatty acid biosynthesis and exhibits in vivo efficacy against skin infections in a mouse model.

microbiology↗