Rory F. Little
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View article: DiscERN: An Automated Genome Mining Tool for the Discovery of Evolutionarily Related Natural Products
DiscERN: An Automated Genome Mining Tool for the Discovery of Evolutionarily Related Natural Products Open
Targeted genome mining to expand known families of natural products is a powerful strategy for discovering bioactive compounds, yet it remains a significant bioinformatics challenge. While tools exist for de novo biosynthetic gene cluster …
View article: Calcium‐Dependent Lipopeptide Antibiotics against Drug‐Resistant Pathogens Discovered via Host‐Dependent Heterologous Expression of a Cloned Biosynthetic Gene Cluster
Calcium‐Dependent Lipopeptide Antibiotics against Drug‐Resistant Pathogens Discovered via Host‐Dependent Heterologous Expression of a Cloned Biosynthetic Gene Cluster Open
Historically, small molecules biosynthesised by bacteria have been an excellent source for antibacterial drugs. Today, however, the rediscovery of known compounds is a significant hurdle to developing new antimicrobials. Here we use a geno…
View article: Calcium‐Dependent Lipopeptide Antibiotics against Drug‐Resistant Pathogens Discovered via Host‐Dependent Heterologous Expression of a Cloned Biosynthetic Gene Cluster
Calcium‐Dependent Lipopeptide Antibiotics against Drug‐Resistant Pathogens Discovered via Host‐Dependent Heterologous Expression of a Cloned Biosynthetic Gene Cluster Open
Historically, small molecules biosynthesised by bacteria have been an excellent source for antibacterial drugs. Today, however, the rediscovery of known compounds is a significant hurdle to developing new antimicrobials. Here we use a geno…
View article: A metagenomic library cloning strategy that promotes high-level expression of captured genes to enable efficient functional screening
A metagenomic library cloning strategy that promotes high-level expression of captured genes to enable efficient functional screening Open
Summary Functional screening of environmental DNA (eDNA) libraries is a potentially powerful approach to discover enzymatic “unknown unknowns”, but is usually heavily biased toward the tiny subset of genes preferentially transcribed and tr…
View article: An intramodular thioesterase domain catalyses chain release in the biosynthesis of a cytotoxic virulence factor
An intramodular thioesterase domain catalyses chain release in the biosynthesis of a cytotoxic virulence factor Open
The bimodular PKS-NRPS BurA has two unusual non-C-terminal thioesterase domains. We show that the intramodular TE-B is responsible for the hydrolytic release of gonyol, an intermediate for the biosynthesis of the virulence factor malleicyp…
View article: Correction: Chain release mechanisms in polyketide and non-ribosomal peptide biosynthesis
Correction: Chain release mechanisms in polyketide and non-ribosomal peptide biosynthesis Open
Correction for ‘Chain release mechanisms in polyketide and non-ribosomal peptide biosynthesis’ by Rory F. Little et al. , Nat. Prod. Rep. , 2021, DOI: 10.1039/d1np00035g.
View article: Chain release mechanisms in polyketide and non-ribosomal peptide biosynthesis
Chain release mechanisms in polyketide and non-ribosomal peptide biosynthesis Open
This review covers the mechanisms of chain release in polyketide and non-ribosomal peptide biosynthesis.
View article: Intracellular complexities of acquiring a new enzymatic function revealed by mass-randomisation of active-site residues
Intracellular complexities of acquiring a new enzymatic function revealed by mass-randomisation of active-site residues Open
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View article: Intracellular complexities of acquiring a new enzymatic function revealed by mass-randomisation of active-site residues
Intracellular complexities of acquiring a new enzymatic function revealed by mass-randomisation of active-site residues Open
No description supplied
View article: Intracellular complexities of acquiring a new enzymatic function revealed by mass-randomisation of active-site residues
Intracellular complexities of acquiring a new enzymatic function revealed by mass-randomisation of active-site residues Open
Selection for a promiscuous enzyme activity provides substantial opportunity for competition between endogenous and newly-encountered substrates to influence the evolutionary trajectory, an aspect that is often overlooked in laboratory dir…
View article: Author response: Intracellular complexities of acquiring a new enzymatic function revealed by mass-randomisation of active-site residues
Author response: Intracellular complexities of acquiring a new enzymatic function revealed by mass-randomisation of active-site residues Open
Article Figures and data Abstract eLife digest Introduction Results Discussion Materials and methods Data availability References Decision letter Author response Article and author information Metrics Abstract Selection for a promiscuous e…
View article: The biosynthetic pathway to tetromadurin (SF2487/A80577), a polyether tetronate antibiotic
The biosynthetic pathway to tetromadurin (SF2487/A80577), a polyether tetronate antibiotic Open
The type I polyketide SF2487/A80577 (herein referred to as tetromadurin) is a polyether tetronate ionophore antibiotic produced by the terrestrial Gram-positive bacterium Actinomadura verrucosospora. Tetromadurin is closely related to the …
View article: Mechanistic Understanding Enables the Rational Design of Salicylanilide Combination Therapies for Gram-Negative Infections
Mechanistic Understanding Enables the Rational Design of Salicylanilide Combination Therapies for Gram-Negative Infections Open
There is a critical need for more-effective treatments to combat multidrug-resistant Gram-negative infections. Combination therapies are a promising strategy, especially when these enable existing clinical drugs to be repurposed as antibio…
View article: Insect‐Associated Bacteria Assemble the Antifungal Butenolide Gladiofungin by Non‐Canonical Polyketide Chain Termination
Insect‐Associated Bacteria Assemble the Antifungal Butenolide Gladiofungin by Non‐Canonical Polyketide Chain Termination Open
Genome mining of one of the protective symbionts ( Burkholderia gladioli ) of the invasive beetle Lagria villosa revealed a cryptic gene cluster that codes for the biosynthesis of a novel antifungal polyketide with a glutarimide pharmacoph…
View article: Insect‐Associated Bacteria Assemble the Antifungal Butenolide Gladiofungin by Non‐Canonical Polyketide Chain Termination
Insect‐Associated Bacteria Assemble the Antifungal Butenolide Gladiofungin by Non‐Canonical Polyketide Chain Termination Open
Genome mining of one of the protective symbionts ( Burkholderia gladioli ) of the invasive beetle Lagria villosa revealed a cryptic gene cluster that codes for the biosynthesis of a novel antifungal polyketide with a glutarimide pharmacoph…
View article: A giant leap in sequence space reveals the intracellular complexities of evolving a new function
A giant leap in sequence space reveals the intracellular complexities of evolving a new function Open
Selection for a promiscuous enzyme activity provides substantial opportunity for competition between endogenous and new substrates to influence the evolutionary trajectory, an aspect that has generally been overlooked in laboratory directe…
View article: Mechanistic understanding enables the rational design of salicylanilide combination therapies for Gram-negative infections
Mechanistic understanding enables the rational design of salicylanilide combination therapies for Gram-negative infections Open
One avenue to combat multidrug-resistant Gram-negative bacteria is the co-administration of multiple drugs (combination therapy), which can be particularly promising if drugs synergize. The identification of synergistic drug combinations, …
View article: Enzymatic Ring Formation in Polyether Tetronate Antibiotic Biosynthesis
Enzymatic Ring Formation in Polyether Tetronate Antibiotic Biosynthesis Open
The formation of rings in carbon backbones is essential for the biological activity of many natural products. The polyether tetronate antibiotics tetronasin, tetronomycin, and tetromadurin (SF2487/A80577) are notable for their ring diversi…