Chad W. Johnston

ORCID: 0000-0002-1988-709X
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About
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Research Areas
  • Microbial Natural Products and Biosynthesis
  • Genomics and Phylogenetic Studies
  • Plant biochemistry and biosynthesis
  • RNA and protein synthesis mechanisms
  • Biochemical and Structural Characterization
  • Peptidase Inhibition and Analysis
  • RNA modifications and cancer
  • Marine Sponges and Natural Products
  • Metabolomics and Mass Spectrometry Studies
  • CRISPR and Genetic Engineering
  • Computational Drug Discovery Methods
  • Microscopic Colitis
  • Metal Extraction and Bioleaching
  • Celiac Disease Research and Management
  • Disaster Management and Resilience
  • Gene Regulatory Network Analysis
  • Minerals Flotation and Separation Techniques
  • Mass Spectrometry Techniques and Applications
  • Nanoparticles: synthesis and applications
  • Microbial Metabolism and Applications
  • Transportation Planning and Optimization
  • Galectins and Cancer Biology
  • Phytoplasmas and Hemiptera pathogens
  • Molecular Communication and Nanonetworks
  • Medicinal Plants and Neuroprotection

Baylor University
2024

Baylor College of Medicine
2022-2024

Massachusetts Institute of Technology
2019-2020

McMaster University
2012-2020

Microbial natural products represent a rich resource of pharmaceutically and industrially important compounds. Genome sequencing has revealed that the majority remain undiscovered, computational methods to connect biosynthetic gene clusters their corresponding therefore have potential revitalize product discovery. Previously, we described PRediction Informatics for Secondary Metabolomes (PRISM), combinatorial approach chemical structure prediction genetically encoded nonribosomal peptides...

10.1093/nar/gkx320 article EN cc-by-nc Nucleic Acids Research 2017-04-21

Abstract Novel antibiotics are urgently needed to address the looming global crisis of antibiotic resistance. Historically, primary source clinically used has been microbial secondary metabolism. Microbial genome sequencing revealed a plethora uncharacterized natural that remain be discovered. However, isolation these molecules is hindered by challenge linking sequence information chemical structures encoded molecules. Here, we present PRISM 4, comprehensive platform for prediction...

10.1038/s41467-020-19986-1 article EN cc-by Nature Communications 2020-11-27

Microbial natural products are an invaluable source of evolved bioactive small molecules and pharmaceutical agents. Next-generation metagenomic sequencing indicates untapped genomic potential, yet high rediscovery rates known metabolites increasingly frustrate conventional product screening programs. New methods to connect biosynthetic gene clusters novel chemical scaffolds therefore critical enable the targeted discovery genetically encoded products. Here, we present PRISM, a computational...

10.1093/nar/gkv1012 article EN cc-by Nucleic Acids Research 2015-10-05

The following article discusses the current emphasis and attention being given to future of emergency management, as well theoretical constructs designed guide research help practitioners reduce disaster. It illustrates that while disaster‐resistant community, disaster‐resilient sustainable development/sustainable hazards mitigation concepts provide many unique advantages for disaster scholarship they fail sufficiently address triggering agents, functional areas, actors, variables,...

10.1111/1540-6210.00178 article EN Public Administration Review 2002-01-01

Significance Natural products and their derivatives are essential to the treatment of many diseases. Ribosomally synthesized posttranslationally modified peptides (RiPPs) a class natural noted for bioactivities. Genome sequencing has revealed that most remain undiscovered, but complexity diversity RiPPs challenged systematic identification these molecules from genomic data. Here, we present an algorithm RiPP structure prediction prokaryotic genomes systematically investigate chemical space...

10.1073/pnas.1609014113 article EN Proceedings of the National Academy of Sciences 2016-10-03

Abstract Bacterial natural products are a diverse and valuable group of small molecules, genome sequencing indicates that the vast majority remain undiscovered. The prediction product structures from biosynthetic assembly lines can facilitate their discovery, but highly automated, accurate, integrated systems required to mine broad spectrum sequenced bacterial genomes. Here we present genome-guided discovery tool automatically predict, combinatorialize identify polyketides nonribosomal...

10.1038/ncomms9421 article EN cc-by Nature Communications 2015-09-28

Significance Natural products form the basis for most drugs in clinical use. Advances genome sequencing and bioinformatic tools have revealed thousands of biosynthetic gene clusters encoding these products. However, linking natural identified by mining to their corresponding untargeted metabolomics data remains a key challenge. Here we present platform, DeepRiPP, which integrates genomic metabolomic automate discovery new ribosomally synthesized posttranslationally modified peptides (RiPPs),...

10.1073/pnas.1901493116 article EN Proceedings of the National Academy of Sciences 2019-12-23

Nonribosomal peptides are highly sought after for their therapeutic applications. As with other natural products, dereplication of known compounds and focused discovery new agents within this class central concerns modern product-based drug discovery. Development a chemoinformatic library-based informatic search strategy products (iSNAP) has been constructed applied to nonribosomal proved useful true nontargeted across spectrum product extracts.

10.1073/pnas.1206376109 article EN Proceedings of the National Academy of Sciences 2012-11-06

Among naturally occurring small molecules, tRNA-derived cyclodipeptides are a class that have attracted attention for their diverse and desirable biological activities. However, no tools available to link cyclodipeptide synthases identified within prokaryotic genome sequences chemical products. Consequently, it is unclear how many genetically encoded represent novel products, which producing organisms should be targeted discovery. We developed pipeline identification classification of...

10.1186/s12864-018-4435-1 article EN cc-by BMC Genomics 2018-01-15

Antibiotic biosynthetic gene clusters (BGCs) produce bioactive metabolites that impart a fitness advantage to their producer, providing mechanism for natural selection. This selection drives antibiotic evolution and adapts BGCs expression in different organisms, potentially clues improve heterologous of antibiotics. Here, we use phage-assisted continuous (PACE) achieve bioactivity-dependent adaptation the BGC bicyclomycin (BCM), facilitating improved production host. proof-of-principle study...

10.1038/s41467-020-18018-2 article EN cc-by Nature Communications 2020-08-21

Expanding our knowledge: Natural lipocyclocarbamate natural products have provided the inspiration for first-in-class synthetic phospholipase inhibitor darapladib, currently in phase III clinical trials treatment of atherosclerosis. Here, we discuss their biosynthesis by a nonribosomal peptide synthetase. As service to authors and readers, this journal provides supporting information supplied authors. Such materials are peer reviewed may be re-organized online delivery, but not copy-edited...

10.1002/cbic.201200598 article EN ChemBioChem 2013-02-10

AbstractGold grains collected from the Rio Saldaña River, Colombia were hundreds of micrometers in size and discoid-ellipse shape. Fourteen 63 contained an iron oxyhydroxide coating that occurred as ca. 50 to 100 nm thick lamina while thicker coatings comprised colloids 200 4 μm diameter. Bacterial-size casts observed throughout intuitively represent relic impressions bacterial cells. The surface textures gold generally smooth with surficial depressions or crevices containing detrital...

10.1080/01490451.2014.935534 article EN Geomicrobiology Journal 2014-08-20

Despite decades of study, large parts the mammalian metabolome remain unexplored. Mass spectrometry-based metabolomics routinely detects thousands small molecule-associated peaks within human tissues and biofluids, but typically only a fraction these can be identified, structure elucidation novel metabolites remains low-throughput endeavor. Biochemical language models have transformed interpretation DNA, RNA, protein sequences, not yet had comparable impact on understanding molecule...

10.1101/2024.11.13.623458 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2024-11-15

Microbial natural products are a crucial source of bioactive molecules and unique chemical scaffolds. Despite their importance, rediscovery known from established productive microbes has led to declining interest, even while emergent genomic data suggest that the majority microbial remain be discovered. Now, new sources must defined in order provide scaffolds for next generation small therapeutic, agricultural, industrial purposes. In this work, we use specialized bioinformatic programs,...

10.1016/j.synbio.2015.12.001 article EN cc-by-nc-nd Synthetic and Systems Biotechnology 2016-02-06

Abstract Antibiotics are essential for modern medicine, but their use drives the evolution of antimicrobial resistance (AMR) that limits long-term efficacy any one drug. To keep pace with AMR and preserve our ability to treat bacterial infections, it is we identify antibiotics new structures targets not affected by clinical resistance. Historically, most developmental candidates have come from microbial natural products, as they feature chemical biological activities been honed over millions...

10.1101/2024.08.13.607837 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2024-08-13

Abstract Nonribosomal depsipeptides are a class of potent microbial natural products, which include several clinically approved pharmaceutical agents. Genome sequencing has revealed large number uninvestigated natural‐product biosynthetic gene clusters. However, while novel informatic search methods to access these clusters have been developed identify peptide depsipeptide detection proven challenging. Herein, we present an improved version our algorithm for products (iSNAP), facilitates the...

10.1002/cbic.201402434 article EN ChemBioChem 2014-12-08

A modern challenge and opportunity exists for in the ability to link genomic metabolomic data, using novel informatic methods find new bioactive natural products.

10.1039/c2md20120h article EN MedChemComm 2012-01-01
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