A5079444904- Microbial Natural Products and Biosynthesis
- Microbial Metabolic Engineering and Bioproduction
- Enzyme Structure and Function
- Plant biochemistry and biosynthesis
- Enzyme Catalysis and Immobilization
- Biotin and Related Studies
- Chemical Synthesis and Analysis
- Carbohydrate Chemistry and Synthesis
- Metabolomics and Mass Spectrometry Studies
- Biochemical and Molecular Research
- Natural product bioactivities and synthesis
- Click Chemistry and Applications
- Mass Spectrometry Techniques and Applications
- Genomics and Phylogenetic Studies
- Plant-Microbe Interactions and Immunity
- Metal complexes synthesis and properties
- Biological Activity of Diterpenoids and Biflavonoids
- RNA and protein synthesis mechanisms
University of California, San Diego
2018-2024
Carbon-carbon bond forming reactions are essential transformations in natural product biosynthesis. During de novo fatty acid and polyketide biosynthesis, β-ketoacyl-acyl carrier protein (ACP) synthases (KS), catalyze this process via a decarboxylative Claisen-like condensation reaction. KSs must recognize multiple chemically distinct ACPs choreograph ping-pong mechanism, often an iterative fashion. Here, we report crystal structures of substrate mimetic bearing complex with the elongating...
Site-specific covalent conjugation offers a powerful tool to identify and understand protein–protein interactions. In this study, we discover that sulfur fluoride exchange (SuFEx) warheads effectively crosslink the Escherichia coli acyl carrier protein (AcpP) with its partner BioF, key pyridoxal 5′-phosphate (PLP)-dependent enzyme in early steps of biotin biosynthesis by targeting tyrosine residue proximal active site. We site MS/MS analysis peptide originating from both partners. further...
Ketosynthases (KSs) catalyze carbon-carbon bond forming reactions in fatty acid synthases (FASs) and polyketide (PKSs). KSs utilize a two-step ping pong kinetic mechanism to carry out an overall decarboxylative thio-Claisen condensation that can be separated into the transacylation reactions. In both steps, acyl carrier protein (ACP) delivers thioester tethered substrates active sites of KSs. Therefore, protein-protein interactions (PPIs) KS-mediated substrate recognition events are required...
The antibiotic cerulenin is a fungal natural product identified as covalent inhibitor of ketosynthases within fatty acid and polyketide biosynthesis. Due to its selective potent inhibitory activity, has found significant utility in multidisciplinary biochemical, biomedical, clinical studies. Although inhibition profile been confirmed, cerulenin's mechanism not fully determined at molecular level, frustrating the drug development related analogues. Herein, we describe use stable isotopic...
Translation of the natural product cerulenin into probe for fluorescent labeling and masked crosslinker to evaluate protein–protein interactivity.
Ketosynthases (KSs) catalyse essential carbon–carbon bond-forming reactions in fatty-acid biosynthesis using a two-step, ping-pong reaction mechanism. In Escherichia coli , there are two homodimeric elongating KSs, FabB and FabF, which possess overlapping substrate selectivity. However, is for the of unsaturated fatty acids (UFAs) required cell survival absence exogenous UFAs. Additionally, has reduced activity towards substrates longer than 12 C atoms, whereas FabF efficiently catalyses...
Outside of their involvement in energy production, mitochondria play a critical role for the cell through access to discrete pathway fatty acid biosynthesis. Despite decades study bacterial synthases (the putative evolutionary mitochondrial precursor), our understanding human biosynthesis remains incomplete. In particular, key carrier protein, acyl protein (mACP), which shuttles substrate intermediates pathway, has not been well-studied part due challenges expression and purification....
Abstract Formation of carbon-carbon bonds via β-ketoacyl-acyl carrier protein (ACP) synthases (KS), are key reactions during de novo fatty acid and polyketide biosynthesis. KSs recognize multiple ACPs choreograph ping-pong mechanisms often in an iterative fashion. Therefore, must limit non-productive protein-protein interactions (PPIs) to achieve high degrees reaction fidelity. To better understand the stereochemical features governing substrate discrimination ACP•KS PPIs, we determined...
Abstract Ketosynthases (KS) catalyse essential carbon-carbon bond forming reactions in fatty acid biosynthesis using a two-step, ping-pong reaction mechanism. In E. coli , there are two homodimeric elongating KSs, FabB and FabF, both of which possess overlapping substrate selectivity. However, is for the unsaturated acids (UFAs) required cell survival absence exogenous UFAs. Additionally, has reduced activity towards substrates longer than 14 carbons, whereas FabF efficiently catalyses...
Abstract Ketosynthases (KSs) catalyze carbon-carbon bond forming reactions in fatty acid synthases (FASs) and polyketide (PKSs). KSs utilize a two-step ping pong kinetic mechanism to carry out an overall decarboxylative thio-Claisen condensation that can be separated into the transacylation reactions. In both steps, acyl carrier protein (ACP) delivers thioester tethered substrates active sites of KSs. Therefore, protein-protein interactions (PPIs) KS-mediated substrate recognition events are...