Publications by authors named "Ryan M Phelan"
Article Synopsis
- Dicarboxylic acids are important chemicals used in making various products like plastics, fragrances, and medications, and there's a shift towards bio-based production due to environmental issues with petroleum sources.
- Current biosynthetic methods mainly produce even-carbon dicarboxylic acids, but there's a need for odd-carbon variations for certain industrial uses.
- The study introduces a new engineering method in E. coli that converts glucose into odd-carbon dicarboxylic acids by using a combination of enzymes from biotin and fatty acid synthesis, aiming for improved industrial production.
Article Synopsis
- Streptomyces bacteria are known for producing natural products and have potential in synthetic biology, but lack genetic tools limits their use compared to E. coli or S. cerevisiae.
- Researchers developed new standardized integration vectors and a method to monitor protein production in Streptomyces venezuelae to enhance metabolic engineering capabilities.
- The study successfully demonstrated the use of these tools by producing bisabolene, a biofuel precursor, showcasing S. venezuelae as a viable host for future projects.
Article Synopsis
- The terminal reductase (R) domain from the MxaA module in Stigmatella aurantiaca Sga15 is involved in producing myxalamide secondary metabolites through a four-electron reduction process.
- Structural and mechanistic insight into R domains has been limited, hindering efforts to redesign them for better performance.
- Researchers successfully obtained crystal structures of the MxaA R domain with and without the NADPH cofactor, using simulations to identify key residues and ultimately developed a variant with enhanced activity for specific substrates.
Article Synopsis
- - The gem-dimethyl groups in natural products enhance the stability of medicinal compounds but pose challenges for their incorporation in modified versions.
- - Researchers studied the polyketide synthase (PKS) mechanisms behind gem-dimethyl group formation in yersiniabactin and epothilone using mass spectrometry.
- - Findings revealed that methylation could happen before the condensation step, challenging previous beliefs, with epothilone's production relying solely on a specific intermediate, dimethylmalonyl-ACP, while yersiniabactin's PKS could methylate at either step.
Article Synopsis
- Recent research has focused on developing sustainable, biologically derived fuels, but less attention has been given to alternative microbes compared to more common ones like E. coli and S. cerevisiae.
- This study investigates the terpene biosynthetic pathway in Streptomyces venezuelae, aiming to enhance production of bisabolene, an advanced biofuel precursor.
- By leveraging insights from the native isoprenoid pathway, the researchers managed to increase bisabolene production nearly five times, demonstrating the potential of this microbe for effective consolidated bioprocessing.
Article Synopsis
- Carbapenems are potent β-lactam antibiotics with a unique ability to resist inactivation by enzymes, and their biosynthesis involves distinct biochemical processes for complex and simple variants.
- The carbapenem synthase enzyme, responsible for crucial final steps in producing simple carbapenems, can process two different substrate forms to create the same active antibiotic.
- Research involving mutagenesis and structural analysis suggests a two-step reaction mechanism rather than a single cycle, involving more complexity in how the enzyme interacts with substrates during the antibiotic generation process.
Article Synopsis
- High-throughput screening techniques have significantly advanced our ability to engineer proteins with new properties, particularly in modifying enzymes for producing various products.
- The researchers developed a high-throughput, genetically regulated screening method for producing β-lactam antibiotics, which uses a green fluorescent protein (GFP) reporter and allows for sensitive detection of different β-lactam subclasses.
- The study successfully demonstrated this method in vivo and provided insights into a key catalytic residue in carbapenem synthase, offering valuable information for future enzyme activity studies and engineering efforts.
Article Synopsis
- *The biosynthesis of the simplest carbapenem requires only three enzymes, while the synthesis of thienamycin is more complex, yet both pathways show potential similarities through gene analysis.
- *Experiments indicate that enzymes CarB and CarA from Pectobacterium and their counterparts in Streptomyces are functionally equivalent, suggesting both pathways start similarly but diverge significantly after the initial steps.
Article Synopsis
- Carbapenems are a crucial class of antibiotics, with over 50 types that differ mainly by C-2 and C-6 side chains, affecting their effectiveness.
- Researchers found that the ThnG and ThnQ enzymes from the thienamycin gene cluster in Streptomyces cattleya play key roles in oxidizing these side chains, enhancing the antibiotic properties of carbapenems.
- Understanding how ThnG and ThnQ work can guide future studies on how carbapenem antibiotics are made, potentially leading to more effective treatments.
Article Synopsis
- The text discusses efficient methods for synthesizing N-acetyl thienamycin and epithienamycin A, focusing on creating three stereocenters in a single reaction.
- It describes how these methods can be used as a model for producing different C-5/C-6 stereoisomers of carbapenems while allowing for independent manipulation of the C-8 stereocenter.
- Additionally, a range of azetidinone precursors has been developed to aid research on the biosynthesis of carbapenem antibiotics.
The current paradigm for tuning synthetic biological systems is through re-engineering system components. Biological systems designed with the inherent ability to be tuned by external stimuli will be more versatile. We engineered Escherichia coli cells to behave as an externally tunable band-pass filter for enzyme activity and small molecules.
View Article and Find Full Text PDFDesign and synthesis of a beta-lactamase activated 5-fluorouracil prodrug.
Bioorg Med Chem Lett
February 2009
Article Synopsis
- An efficient method for creating a prodrug that combines 5-fluorouracil with cephalosporin is presented, aimed at treating colorectal and other cancers through targeted therapies.
- This prodrug remains stable in water until it is activated by a specific enzyme called beta-lactamase (betaL).
- The study measured the kinetic properties of the prodrug when exposed to a specific strain of bacteria, providing valuable data for future testing against cancer cells in lab and animal studies.