A5060697184- Pharmacogenetics and Drug Metabolism
- Enzyme Catalysis and Immobilization
- Microbial Metabolic Engineering and Bioproduction
- Protein Structure and Dynamics
- Innovative Microfluidic and Catalytic Techniques Innovation
- Genomics and Phylogenetic Studies
- Computational Drug Discovery Methods
- Mycobacterium research and diagnosis
- Glycosylation and Glycoproteins Research
- Asymmetric Hydrogenation and Catalysis
- Lipid metabolism and biosynthesis
- Biofuel production and bioconversion
- Steroid Chemistry and Biochemistry
- Genomic variations and chromosomal abnormalities
- Prenatal Screening and Diagnostics
- Plant Parasitism and Resistance
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- Biochemical and Molecular Research
- Allelopathy and phytotoxic interactions
- Statistical Methods in Clinical Trials
- Plant and animal studies
- Renal Transplantation Outcomes and Treatments
- Drug Transport and Resistance Mechanisms
The University of Queensland
2017-2024
AstraZeneca (Sweden)
2024
Gallipoli Medical Research Foundation
2023
Ancestral sequence reconstruction is a technique that gaining widespread use in molecular evolution studies and protein engineering. Accurate requires the ability to handle appropriately large numbers of sequences, as well insertion deletion (indel) events, but available approaches exhibit limitations. To address these limitations, we developed Graphical Representation Sequence Predictions (GRASP), which efficiently implements maximum likelihood methods enable inference ancestors families...
Abstract Selective, one‐step C−H activation of fatty acids from biomass is an attractive concept in sustainable chemistry. Biocatalysis has shown promise for generating high‐value hydroxy acids, but to date enzyme discovery relied on laborious screening and produced limited hits, which predominantly oxidise the subterminal positions acids. Herein we show that ancestral sequence reconstruction (ASR) effective tool explore sequence‐activity landscape a family multidomain, self‐sufficient P450...
Abstract The cytochrome P450 family 1 enzymes (CYP1s) are a diverse of hemoprotein monooxygenases, which metabolize many xenobiotics including numerous environmental carcinogens. However, their historical function and evolution remain largely unstudied. Here we investigate CYP1 via the reconstruction characterization vertebrate ancestors. Younger ancestors extant forms generally demonstrated higher activity toward typical xenobiotic steroid substrates than older ancestors, suggesting...
Abstract The Cytochrome P450s (CYPs) enzyme family metabolizes ∼80% of small molecule drugs. Variants in CYPs can substantially alter drug metabolism, leading to improper dosing and severe adverse reactions. Due low sequence conservation, predicting variant effects across is challenging. Even closely related like CYP2C9 CYP2C19, which share 92% amino acid identity, display distinct phenotypic properties. Using Variant Abundance by Massively Parallel sequencing (VAMP-seq), we measured the...
Summary The strigolactone (SL) class of phytohormones shows broad chemical diversity, the functional importance which remains to be fully elucidated, along with enzymes responsible for diversification SL structure. Here we explore evolution highly conserved CYP711A P450 family, members catalyze several key monooxygenation reactions in pathway. Ancestral sequence reconstruction was utilized infer ancestral sequences based on a comprehensive set extant CYP711 sequences. Eleven enzymes,...
Abstract Ancestral sequence reconstruction is a technique that gaining widespread use in molecular evolution studies and protein engineering. Accurate requires the ability to handle appropriately large numbers of sequences, as well insertion deletion (“indel”) events, but available approaches exhibit limitations. To address these limitations, we developed Graphical Representation Sequence Predictions (GRASP), which efficiently implements maximum likelihood methods enable inference ancestors...
Cytogenetic examination of a dysmorphic infant with multiple congenital abnormalities revealed possible de novo interstitial deletion in the long arm chromosome 16. Conclusive proof was obtained by flow karyotype analysis patient and both parents, which showed that deleted segment approximately 7000 kb size.
Abstract The structure of metabolites drug candidates must frequently be characterised during discovery and development. However, synthesising with the correct stereoselective modifications can challenging for chemically complex parent compounds. Biocatalysis using human drug‐metabolising enzymes, such as cytochrome P450 2D6 (CYP2D6) is an alternative to chemical synthesis. most natural enzymes are unstable have poor efficiency, limiting yields in preparative biotransformations. aim this...
Detailed structural characterization of small molecule metabolites is desirable during all stages drug development, and often relies on the synthesis metabolite standards. However, introducing changes into already complex, highly functionalized molecules both regio- stereo-selectively can be challenging using purely chemical approaches, delays pipeline. An alternative to use cytochrome P450 enzymes (P450s) that produce in vivo, taking advantage enzyme's inherently chiral active site achieve...
Ancestral sequence reconstruction can be used to obtain highly thermostable catalysts of fatty acid hydroxylation.
Abstract Selective, one‐step C−H activation of fatty acids from biomass is an attractive concept in sustainable chemistry. Biocatalysis has shown promise for generating high‐value hydroxy acids, but to date enzyme discovery relied on laborious screening and produced limited hits, which predominantly oxidise the subterminal positions acids. Herein we show that ancestral sequence reconstruction (ASR) effective tool explore sequence‐activity landscape a family multidomain, self‐sufficient P450...
Abstract Cytochrome P450s (CYPs) are a family of enzymes responsible for metabolizing nearly 80% small molecule drugs. Variants in CYPs can substantially alter drug metabolism, which may result improper dosing and severe adverse reactions. have low sequence conservation, making it difficult to anticipate whether variant effects measured one CYP extend others based on alone. Even closely related CYPs, like CYP2C9 its closest homolog CYP2C19, distinct phenotypic properties despite sharing 92%...
Selective, one-step C-H activation of fatty acids from biomass is an attractive concept in sustainable chemistry. Biocatalysis has shown promise for generating high-value hydroxy but to date enzyme discovery relied on laborious screening and produced limited hits, which predominantly oxidise the sub-terminal positions acids. Here we show that ancestral sequence reconstruction (ASR) effective tool explore sequence-activity landscape a family multi-domain, self-sufficient P450 monooxygenases....
Producing sufficient amounts or stable, properly folded protein is an essential prerequisite for crystallization, especially challenging targets such as membrane proteins.However many proteins in their native form show limited stability and are refractory to expression recombinant hosts.Over the last several years, ancestral sequence reconstruction has (ASR) emerged a useful tool by which engineers crystallographers can obtain highly robust forms of interest, often also expressed at...