A5003685013- Pharmacogenetics and Drug Metabolism
- Enzyme Catalysis and Immobilization
- Hormonal Regulation and Hypertension
- Cancer Treatment and Pharmacology
- Microbial Metabolic Engineering and Bioproduction
- Asymmetric Hydrogenation and Catalysis
- Biochemical and Molecular Research
- Lipid metabolism and biosynthesis
- Metabolomics and Mass Spectrometry Studies
- Hormonal and reproductive studies
- Plant biochemistry and biosynthesis
- Estrogen and related hormone effects
- Drug Transport and Resistance Mechanisms
- Biosimilars and Bioanalytical Methods
The University of Queensland
2016-2024
AstraZeneca (Sweden)
2020
University of Rostock
2016
Mitochondrial cytochromes P450 presumably originated from a common microsomal ancestor. However, it is still unknown how ancient mitochondrial P450s were able to retain their oxygenase function following relocation the matrix and later emerged as enzymes specialized for steroid hormone biosynthesis in vertebrates. Here, we used approach of ancestral sequence reconstruction (ASR) resurrect CYP11A1 characterize unique biochemical properties. Two variants, CYP11A_Mammal_N101 CYP11A_N1, well an...
NADPH‐cytochrome P450 reductase (CPR) is the natural redox partner of microsomal cytochrome enzymes. CPR shows a stringent preference for NADPH over less expensive cofactor, NADH, economically limiting its use as biocatalyst. The complexity cofactor‐linked protein dynamics and incomplete understanding interaction with both cofactors electron acceptors present challenges successful rational engineering enhanced activity NADH. Here, we report evolution approach to enhance in which mutations...
Oxygen surrogates (OSs) have been used to support cytochrome P450 (P450) enzymes for diverse purposes in drug metabolism research, including reaction phenotyping, mechanistic and inhibition studies, studies of redox partner interactions, avoid the need NADPH or a partner. They also engineering P450s more cost-effective, NADPH-independent biocatalysis. However, despite their broad application, little is known preference individual different OSs substrate dependence OS-supported activity....
Ancestral sequence reconstruction can be used to obtain highly thermostable catalysts of fatty acid hydroxylation.
The recombinant pig liver esterase catalyzed hydrolysis of cis-1,4-diacetoxy-2-cyclopentene forming (1S,4R)-4-hydroxy-2-cyclopentenyl acetate was investigated and realized at preparative scale. Relevant reaction conditions were examined optimized to achieve full conversion with an enantiomeric excess about 86% ee. Enantiopure product then obtained after enantioselective crystallization, which required further studies the solid phase behavior, including its binary melting point diagram.
Abstract Cytochrome P450 enzymes (P450s) are highly desirable catalysts for the regio‐ and stereo‐selective, late‐stage functionalization of pharmaceuticals other fine chemicals. Recently, resurrected ancestors drug‐metabolizing P450s were shown to be thermostable expressed in high yield, while retaining similar substrate specificity extant forms. However, they still rely on NADPH cytochrome reductase (CPR) enable catalysis oxidative transformations. To identify an alternative support...