Gregory L. Challis

Molecular basis for depsipeptide HDAC inhibitor combinatorial biosynthesis

The paper identifies a novel subunit docking mechanism in depsipeptide HDAC inhibitor biosynthesis using gene proximity searching and experimental validation.

Substrate scope and catalytic mechanism of α, β-epoxyketone synthase EpnF illuminated by in-situ esterase-mediated deprotection

This paper develops an esterase-mediated strategy to generate unstable substrates for EpnF, revealing its broad substrate tolerance and catalytic mechanism for epoxyketone synthesis.

Cryptic starter amidation in antibiotic biosynthesis by trans-acyltransferase polyketide synthases

The paper reveals a cryptic amidation mechanism in gladiolin biosynthesis involving a trans-acyltransferase, ACP, and asparagine synthetase homolog.

PARAS: high-accuracy machine-learning of substrate specificities in nonribosomal peptide synthetases

Random forest predictors PARAS and PARASECT, trained on 3,653 curated adenylation domains, outperform earlier NRPS substrate predictors and correctly assigned L-Trp to an unusual tryptopeptin synthetase domain.

Discovery of late intermediates in methylenomycin biosynthesis active against drug-resistant Gram-positive bacterial pathogens

This study identifies key biosynthetic enzymes in methylenomycin production and discovers more potent intermediates active against drug-resistant Gram-positive bacteria.

Bioinformatics-based stereochemical elucidation of MM 46115: an unusual antiviral spirotetronate that inhibits clathrin-mediated endocytosis

This paper identifies and characterizes pellemicin, a spirotetronate with antiviral activity against influenza A and B viruses by inhibiting clathrin-mediated endocytosis.

Discovery and Biosynthetic Origin of 4,4'-Dihydroxy-3,3',5,5' Tetrachlorobenzophenone Produced by the Clinical Isolate Burkholderia oklahomensis

The paper identifies a novel polychlorinated compound produced by Burkholderia oklahomensis and proposes its biosynthetic pathway.

An O-acetylated derivative of piericidin A1 produced by Kitasatospora sp. A2-31 has potent activity against the cacao mirid bug, Helopeltis bakeri Poppius

The paper identifies a novel acetylated derivative of piericidin A1 from Kitasatospora sp. A2-31 that shows 100% mortality against the cacao mirid bug.

Nitrogen deletion in the biosynthesis of HDAC-targeting anticancer drugs

The paper investigates nitrogen deletion in the biosynthesis of HDAC-targeting anticancer drugs, showing its importance for bioactivity and revealing the enzymatic mechanisms involved.

Prediction of gene cluster function based on transcriptional regulatory networks uncovers a novel locus required for desferrioxamine B biosynthesis

Metagenomic domain substitution for the high-throughput modification of non-ribosomal peptide analogues

The paper uses metagenomic domain substitution to generate novel non-ribosomal peptides by screening over 1,000 domains in a pyoverdine NRPS, resulting in 16 distinct products.

clusterTools: Proximity Searches For Functional Elements To Identify Putative Biosynthetic Gene Clusters

clusterTools identifies putative biosynthetic gene clusters by querying functional elements in genomic data.