A5016300087- Microbial Natural Products and Biosynthesis
- Genomics and Phylogenetic Studies
- Biochemical and Structural Characterization
- Civil and Structural Engineering Research
- Plant biochemistry and biosynthesis
- Microbial Community Ecology and Physiology
- X-ray Diffraction in Crystallography
- Metabolomics and Mass Spectrometry Studies
- Crystallization and Solubility Studies
- Structural Analysis of Composite Materials
- Engineering and Materials Science Studies
- Marine Sponges and Natural Products
- Bacterial Identification and Susceptibility Testing
- Phytochemical compounds biological activities
- Glycosylation and Glycoproteins Research
- Plant Gene Expression Analysis
- Gene expression and cancer classification
- Crystallography and molecular interactions
- Structural Load-Bearing Analysis
- Species Distribution and Climate Change
- Liver physiology and pathology
- RNA and protein synthesis mechanisms
- Plant-Microbe Interactions and Immunity
- 3D Printing in Biomedical Research
- Drug-Induced Hepatotoxicity and Protection
University of Michigan–Ann Arbor
2021-2024
Whitehead Institute for Biomedical Research
2017-2018
Moscow Institute of Thermal Technology
2017
Salk Institute for Biological Studies
2015-2016
University of California, San Diego
2009-2015
Howard Hughes Medical Institute
2015
Scripps Institution of Oceanography
2010-2014
University of Montana
2009-2013
Medtronic (Germany)
1982
Integrating the governing chemistry with genomics and phenotypes of microbial colonies has been a “holy grail” in microbiology. This work describes highly sensitive, broadly applicable, cost-effective approach that allows metabolic profiling live directly from Petri dish without any sample preparation. Nanospray desorption electrospray ionization mass spectrometry (MS), combined alignment MS data molecular networking, enabled monitoring metabolite production diverse bacterial genera,...
Significance Microbes have the genetic capacity to produce large numbers of specialized compounds, yet only a small fraction these in laboratory. Here we introduce platform that allows efficient production natural product molecules from uncharacterized gene collections. We used transformation-associated recombination yeast directly clone and express an orphan biosynthetic cluster for lipopeptide antibiotic taromycin A. With this direct cloning approach, single genomic capture expression...
The ability to correlate the production of specialized metabolites genetic capacity organism that produces such molecules has become an invaluable tool in aiding discovery biotechnologically applicable molecules. Here, we accomplish this task by matching molecular families with gene cluster families, making these correlations 60 microbes at one time instead connecting molecule a time, as how it is traditionally done. We can through use nanospray desorption electrospray ionization MS/MS,...
The anti-neoplastic agent didemnin B from the Caribbean tunicate Trididemnum solidum was first marine drug to be clinically tested in humans. Because of its limited supply and complex cyclic depsipeptide structure, considerable challenges were encountered during B's development that continue limit aplidine (dehydrodidemnin B), which is currently being evaluated numerous clinical trials. Herein we show didemnins are bacterial products produced by α-proteobacteria Tistrella mobilis bauzanensis...
Ribosomally synthesized and posttranslationally modified peptides (RiPPs), especially from microbial sources, are a large group of bioactive natural products that promising source new (bio)chemistry bioactivity.1 In light exponentially increasing genome databases improved mass spectrometry (MS)-based metabolomic platforms, there is need for computational tools connect product genotypes predicted sequences with their corresponding chemotypes data sets. Here, we introduce RiPPquest, tandem...
Significance Glycosyl groups function as essential chemical mediators of molecular interactions in cells and on cellular surfaces. Microbes integrate carbohydrates into secondary metabolism to produce glycosylated natural products (GNPs) that may communication defense. Many metabolites are important pharmaceutical agents. Herein, we introduce glycogenomics a new genome-mining method links metabolomics genomics for the rapid identification characterization bioactive microbial GNPs....
ABSTRACT Potatoes are cultivated in southwest Greenland without the use of pesticides and with limited crop rotation. Despite fact that plant-pathogenic fungi present, no severe-disease outbreaks have yet been observed. In this report, we document a potato soil at Inneruulalik southern is suppressive against Rhizoctonia solani Ag3 uncover antifungal mechanism highly potent biocontrol bacterium, Pseudomonas fluorescens In5, isolated from soil. A combination molecular genetics, genomics,...
Nonribosomal peptides (NRPs) such as vancomycin and daptomycin are among the most effective antibiotics. While NRPs biomedically important, computational techniques for sequencing these still in their infancy. The recent emergence of mass spectrometry NRP analysis (capable an from small amounts nonpurified material) revealed enormous diversity NRPs. However, many have nonlinear structure (e.g., cyclic or branched-cyclic peptides), standard de novo tools (developed linear peptides) not...
Abstract The use of genome sequences has become routine in guiding the discovery and identification microbial natural products their biosynthetic pathways. In silico prediction molecular features, such as metabolic building blocks, physico‐chemical properties or biological functions, from orphan gene clusters opened up characterization many new chemo‐ genotypes mining approaches. Here, we guided our two predicted enediyne pathways Salinispora tropica CNB‐440 by a DNA interference bioassay to...
Here, we described the discovery of anti-infective agent arylomycin and its biosynthetic gene cluster in an industrial daptomycin producing strain Streptomyces roseosporus. This was accomplished via use MALDI imaging mass spectrometry (IMS) along with peptidogenomic approach which have expanded to short sequence tagging (SST) herein. Using IMS, observed that prior production daptomycin, a ions (1-3) produced by S. roseosporus correlated well decreased staphylococcal cell growth. With further...
Sesquiterpene scaffolds are the core backbones of many medicinally and industrially important natural products. A plethora sesquiterpene synthases, widely present in bacteria, fungi, plants, catalyze formation these intricate structures often with multiple stereocenters starting from linear farnesyl diphosphate substrates. Recent advances next-generation sequencing metabolomics technologies have greatly facilitated gene discovery for synthases. However, a major bottleneck limits biochemical...
The plant kingdom contains vastly untapped natural product chemistry, which has been traditionally explored through the activity-guided approach. Here, we describe a gene-guided approach to discover and engineer class of ribosomal peptides, branched cyclic lyciumins. Initially isolated from Chinese wolfberry Lycium barbarum, lyciumins are protease-inhibiting peptides featuring an N-terminal pyroglutamate macrocyclic bond between tryptophan-indole nitrogen glycine α-carbon. We report...
Abstract Even though raw mass spectrometry data is information rich, the vast majority of underutilized. The ability to interrogate these rich datasets handicapped by limited capability and flexibility existing software. We introduce Mass Spec Query Language (MassQL) that addresses issues enabling an expressive set patterns be queried directly from data. MassQL open-source query language for flexible spectrometer manufacturer-independent mining MS envision flexibility, scalability, ease use...
Moroidin is a bicyclic plant octapeptide with tryptophan side-chain cross-links, originally isolated as pain-causing agent from the Australian stinging tree Dendrocnide moroides. and its analog celogentin C, derived Celosia argentea, are inhibitors of tubulin polymerization and, thus, lead structures for cancer therapy. However, low isolation yields source plants challenging organic synthesis hinder moroidin-based drug development. Here, we present biosynthesis an alternative route to...
Abstract Recent analyses of public microbial genomes have found over a million biosynthetic gene clusters, the natural products majority which remain unknown. Additionally, GNPS harbors billions mass spectra without known structures and genes. We bridge gap between large-scale genome mining spectral datasets for product discovery by developing HypoRiPPAtlas, an Atlas hypothetical structures, is ready-to-use in silico database search tandem spectra. HypoRiPPAtlas constructed using seq2ripp,...
Understanding the distribution of hundreds thousands plant metabolites across kingdom presents a challenge. To address this, we curated publicly available LC-MS/MS data from 19,075 extracts and developed plantMASST reference database encompassing 246 botanical families, 1,469 genera, 2,793 species. This taxonomically focused facilitates exploration plant-derived molecules using tandem mass spectrometry (MS/MS) spectra. tool will aid in drug discovery, biosynthesis, (chemo)taxonomy,...