About

Dr. Bradley S. Moore is a Distinguished Professor at the Skaggs School of Pharmacy and Pharmaceutical Sciences, with a research focus on understanding the fundamental mechanisms and pathways involved in microbial production of antibiotics, anticancer agents, and other bioactive natural products, particularly from marine microorganisms. His laboratory employs sophisticated approaches at the chemistry-biology interface, including heterologous biosynthesis, mutasynthesis, chemoenzymatic total synthesis, genome mining, and biochemical analysis performed both in vitro and in vivo. His work emphasizes marine microbes, which harbor promising natural compounds such as salinosporamide A, didemnin, taromycin, marinopyrrole, domoic acid, and kainic acid, contributing significantly to drug discovery efforts. Dr. Moore has pioneered biosynthesis and bioengineering of marine natural product drug leads, developed genome mining and synthetic biology techniques for producing new antibiotic and anticancer agents, and elucidated mechanisms of biosynthesis and resistance enzymes. His contributions have advanced understanding of natural product biosynthesis, including decoding neurotoxins from harmful algal blooms, and his research continues to expand the potential of microbial biodiversity as a resource for novel therapeutics.

Research topics

• Computer Science
• Bioinformatics
• Biochemistry
• Computational biology
• Biology
• Ecology
• Data science
• Genetics

Selected publications

• Emerging Investigators at the Forefront of Natural Products Research

  Journal of Natural Products · 2025-04-25

  editorial1st authorCorresponding
  PublisherDOI

• Discovery of acylsulfenic acid-featuring natural product sulfenicin and characterization of its biosynthesis

  Nature Chemistry · 2025-05-20 · 8 citations

  articleOpen access
  PublisherOA PDFDOI

• Growth-coupled microbial biosynthesis of the animal pigment xanthommatin

  Nature Biotechnology · 2025-11-03 · 5 citations

  articleSenior authorCorresponding
  PublisherDOI

• Diversification of diterpene biosynthesis occurred early in octocoral evolution

  Proceedings of the National Academy of Sciences · 2025-11-26 · 2 citations

  articleOpen accessSenior authorCorresponding

  Octocorals are the major source of marine-derived bioactive terpenoids. However, the vast majority of explored chemistry is known from shallow-water species, leaving deep-sea octocorals largely unexplored. Recent genomic work uncovered terpene biosynthetic pathways encoded in octocoral genomes, enabling deeper investigation into the evolution and ecological distribution of these compounds. Here, we collected nine deep-sea octocoral specimens representing both taxonomic orders and profiled their terpenoid chemistry. These samples revealed extensive diversity in sesquiterpene scaffolds, along with repeated detection of five widespread structural families of diterpenes (xeniaphyllene-, cembrene B-, elisabethatriene-, cembrene A-, and klysimplexin R; collectively, "XBECK-type" diterpenoids). Phylogenetic analysis of terpene cyclase (TC) sequences from these samples, combined with publicly available sequences and functional characterization of selected genes, indicated that most TC genes encode functionally diverse sesquiterpene cyclases that corresponded to deeply rooted taxonomic origins, rather than biochemical function. We further identified five monophyletic clades, each comprising isofunctional enzymes that produce precursors for distinct XBECK-type diterpenoids and showing broad representation across octocoral taxa. These findings suggest that diterpenoid biosynthesis evolved early in coral evolution, with the last common ancestor already possessing multiple functionally distinct TC enzymes. Our results establish terpenoid production as an ancient, central trait of octocorals, irrespective of habitat, thereby highlighting the tremendous potential of deep-sea corals as sources for bioactive terpenoids. Finally, these findings raise intriguing questions about the evolutionary origins of these pathways within early cnidarians and across animal phyla more broadly.

  PublisherOA PDFDOI

• Domoic acid biosynthesis and genome expansion in <i>Nitzschia navis-varingica</i>

  mBio · 2025-10-30 · 1 citations

  articleOpen accessSenior author

  ABSTRACT Production of the neurotoxin domoic acid (DA) by benthic diatom Nitzschia navis-varingica poses considerable health and economic concerns. In this study, we employed whole genome sequencing and transcriptomic analyses of regionally distinct N. navis-varingica strains to unravel the genomic underpinnings of DA biosynthesis. Our analyses revealed sizable genomes—characterized by an abundance of repetitive elements and noncoding DNA—that exceed the size of any other pennate diatoms. Central to our findings is the discovery of an expanded domoic acid biosynthesis ( dab ) gene cluster, spanning over 60 kb and marked by a unique organization that includes core genes interspersed with additional genetic elements. Phylogenetic and syntenic comparisons indicate that transposition events may have driven the expansion and reorganization of this cluster. Biochemical assays validated that the kainoid synthase encoded by dabC catalyzes the formation of isodomoic acid B, thereby establishing a distinct chemotype in contrast to the DA profiles of planktonic diatoms. These results highlight the evolutionary trajectory of DA biosynthesis in diatoms and potential advantages conferred by genome expansion and enzyme diversification in dynamic marine environments. IMPORTANCE Domoic acid (DA) is a potent neurotoxin produced by marine micro- and macroalgae problematic to fisheries and toxic to humans and animals. Our study elucidates the molecular mechanisms underlying DA production in the widespread Western Pacific benthic diatom, Nitzschia navis-varingica . Genomic and biochemical insights add information to our understanding of the evolution of toxin production across diverse phyla and also fill a gap in the knowledge of secondary metabolism in marine diatoms. These findings provide a genetic framework for identifying toxin production and its impacts in the benthos of vulnerable, coastal ecosystems.

  PublisherDOI

• Structural and biochemical basis for cannabinoid cyclase activity in marine bacterial flavoenzymes

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-07

  preprintOpen accessSenior authorCorresponding

  The marine bacterial flavoenzymes Clz9 and Tcz9 can process cannabigerolic acid (CBGA) to the minor cannabinoid, cannabichromenic acid (CBCA), however, the mechanistic details of this extrinsic transformation are still obscure. Here, we report a thorough analysis of CBCA-formation by Clz9 and Tcz9 through high-resolution crystallographic characterization, biochemical analysis, and spectroscopic interrogation. Our work reveals that Clz9 and Tcz9 use different biochemical mechanisms from Cannabis cyclases and each other in their production of CBCA. Collection of a high-resolution substrate-bound structure, the first for any cannabinoid cyclase, provides key insights into how active site architecture affects substrate binding and stereoselectivity. Engineering approaches improve the stereoselectivity of CBCA formation by Clz9 and Tcz9, providing access to (R) and (S)-CBCA. Collectively, our work advances understanding of enzymatic cannabinoid formation and cements Clz9 and Tcz9 as two unique members of the BBE-like enzyme family with encouraging potential for biocatalytic cannabinoid production applications.

  PublisherOA PDFDOI

• Metagenomic Identification of Brominated Indole Biosynthetic Machinery from Cyanobacteria

  Journal of Natural Products · 2025-07-10 · 1 citations

  articleOpen accessCorresponding

  Halogenated indole natural products have been isolated from a variety of organisms, including plants, marine algae, marine invertebrates, and bacteria. Aquatic cyanobacteria, in particular, are rich producers of brominated indoles, but their cognate biosynthetic enzymes have only been successfully linked in a limited number of natural products, such as the eagle-killing toxin aetokthonotoxin (AETX). The biosynthetic pathway for AETX involves five enzymes, two of which were previously undescribed due to incomplete annotations as hypothetical proteins. Our recent elucidation of AETX biosynthesis established functions of the two previously unknown proteins as enzymes responsible for tryptophan halogenation (AetF) and nitrile synthesis (AetD). Given their sequence novelty, we queried metagenomic data sets for these two enzymes and identified two new cyanobacterial haloindole biosynthetic gene clusters (BGCs) from marine sediment in Moorea, French Polynesia, and soil-derived samples in Maunawili Falls, Hawaii. We characterized the recovered BGCs by biochemically validating a new AetF homologue that exclusively halogenates free indole, rather than tryptophan as observed in AETX biosynthesis, and a new AetD homologue that harbors distinct substrate preferences, expanding the scope of nitrile biosynthesis. Additional characterization of core and accessory enzymes within these AETX-like BGCs highlights the breadth and diversity of haloindole biosynthetic machinery in cyanobacteria.

  PublisherOA PDFDOI

• Domoic acid biosynthesis and genome expansion in <i>Nitzschia navis-varingica</i>

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-24 · 1 citations

  preprintOpen accessSenior authorCorresponding

  ABSTRACT Production of the neurotoxin domoic acid (DA) by benthic diatom Nitzschia navis-varingica poses considerable health and economic concerns. In this study, we employed whole genome sequencing and transcriptomic analyses of regionally distinct N. navis-varingica strains to unravel the genomic underpinnings of DA biosynthesis. Our analyses revealed sizable genomes—characterized by an abundance of repetitive elements and noncoding DNA—that exceed the size of any other pennate diatoms. Central to our findings is the discovery of an expanded domoic acid biosynthesis ( dab ) gene cluster, spanning over 60 kb and marked by a unique organization that includes core genes interspersed with additional genetic elements. Phylogenetic and syntenic comparisons indicate that transposition events may have driven the expansion and reorganization of this cluster. Biochemical assays validated that the kainoid synthase encoded by dabC catalyzes the formation of isodomoic acid B, thereby establishing a distinct chemotype in contrast to the DA profiles of planktonic diatoms. These results highlight the evolutionary trajectory of DA biosynthesis in diatoms and potential advantages conferred by genome expansion and enzyme diversification in dynamic marine environments. IMPORTANCE Domoic acid (DA) is a potent neurotoxin produced by marine micro- and macroalgae problematic to fisheries and toxic to humans and animals. Our study elucidates the molecular mechanisms underlying DA production in the widespread Western Pacific benthic diatom, Nitzschia navis-varingica . Genomic and biochemical insights add information to our understanding of the evolution of toxin production across diverse phyla and also fill a gap in the knowledge of secondary metabolism in marine diatoms. These findings provide a genetic framework for identifying toxin production and its impacts in the benthos of vulnerable, coastal ecosystems.

  PublisherOA PDFDOI

• Chromosome-Level Genome Assembly and Annotation of <i>Corallium rubrum</i>: A Mediterranean Coral Threatened by Overharvesting and Climate Change

  Genome Biology and Evolution · 2025-02-01 · 2 citations

  articleOpen access

  Reference genomes are key resources in biodiversity conservation. Yet, sequencing efforts are not evenly distributed across the tree of life raising concerns over our ability to enlighten conservation with genomic data. Good-quality reference genomes remain scarce in octocorals while these species are highly relevant targets for conservation. Here, we present the first annotated reference genome in the red coral, Corallium rubrum (Linnaeus, 1758), a habitat-forming octocoral from the Mediterranean and neighboring Atlantic, impacted by overharvesting and anthropogenic warming-induced mass mortality events. Combining long reads from Oxford Nanopore Technologies (ONT), Illumina paired-end reads for improving the base accuracy of the ONT-based genome assembly, and Arima Hi-C contact data to place the sequences into chromosomes, we assembled a genome of 532 Mb (20 chromosomes, 309 scaffolds) with contig and scaffold N50 of 1.6 and 18.5 Mb, respectively. Fifty percent of the sequence (L50) was contained in seven superscaffolds. The consensus quality value of the final assembly was 42, and the single and duplicated gene completeness reported by BUSCO was 86.4% and 1%, respectively (metazoa_odb10 database). We annotated 26,348 protein-coding genes and 34,548 noncoding transcripts. This annotated chromosome-level genome assembly, one of the first in octocorals and the first in Scleralcyonacea order, is currently used in a project based on whole-genome resequencing dedicated to the conservation and management of C. rubrum.

  PublisherOA PDFDOI

• Single-Enzyme Conversion of Tryptophan to Skatole and Cyanide Expands the Mechanistic Competence of Diiron Oxidases

  Journal of the American Chemical Society · 2025-02-12 · 13 citations

  articleOpen accessSenior authorCorresponding

  Skatole is a pungent heterocyclic compound derived from the essential amino acid l-tryptophan by bacteria in the mammalian digestive tract. The four-step anaerobic conversion of tryptophan to skatole is well-established; though, to date, no aerobic counterpart has been reported. Herein, we report the discovery of the oxygen-dependent skatole synthase SktA that single-handedly converts 5-bromo-l-tryptophan to 5-bromoskatole, obviating the need for a multienzyme process. SktA is part of a three-gene biosynthetic gene cluster (BGC) in the cyanobacterium Nostoc punctiforme NIES-2108 and functions as a nonheme diiron enzyme belonging to the heme oxygenase-like domain-containing oxidase (HDO) superfamily. Our detailed biochemical analyses revealed cyanide and bicarbonate as biosynthetic coproducts, while stopped-flow experiments showed the hallmark formation of a substrate-triggered peroxo Fe2(III) intermediate. Overall, this work unravels an alternative pathway for converting tryptophan to skatole while also expanding the functional repertoire of HDO enzymes.

  PublisherDOI

Recent grants

• Biosynthesis of marine terpenoid natural products

  NIH · $1.6M · 2023–2027

• Natural sources and microbial transformation of marine halogenated pollutants

  NSF · $767k · 2018–2024

• Natural Product Genome Mining

  NIH · $5.8M · 2009–2026

• Scripps Center for Oceans and Human Health

  NSF · $4.1M · 2013–2019

• Biosynthesis of Marine Polyketide Antibiotics

  NIH · $565k · 2000–2017

Frequent coauthors

• Paul R. Jensen

  University of California, San Diego

  135 shared

• Pieter C. Dorrestein

  University of California, San Diego

  134 shared

• Joseph P. Noel

  Salk Institute for Biological Studies

  88 shared

• Shaun M. K. McKinnie

  University of California, Santa Cruz

  82 shared

• William Fenical

  Scripps Institution of Oceanography

  79 shared

• Vinayak Agarwal

  IIT@MIT

  68 shared

• Jonathan R. Chekan

  University of North Carolina at Greensboro

  66 shared

• Longkuan Xiang

  Human BioMolecular Research Institute

  61 shared

Awards & honors

• ASP Matt Suffness New Investigator Award (2001)
• Fellow of the Royal Society for Chemistry (2010)
• President of ASP (2013-2014)
• ACS Arthur C. Cope Scholar Award (2013)
• ETH Visiting Faculty Award (2014)