Understanding Cytochrome P450 Enzyme Substrate Inhibition and Prospects for Elimination Strategies.

Cytochrome P450 (CYP450) enzymes, which are widely distributed and pivotal in various biochemical reactions, catalyze diverse processes such as hydroxylation, epoxidation, dehydrogenation, dealkylation, nitrification, and bond formation. These enzymes have been applied in drug metabolism, antibiotic production, bioremediation, and fine chemical synthesis. Recent research revealed that CYP450 catalytic kinetics deviated from the classic Michaelis-Menten model. A notable substrate inhibition phenomenon that affects the catalytic efficiency of CYP450 at high substrate concentrations was identified. However, the substrate inhibition of various reactions catalyzed by CYP450 enzymes have not been comprehensively reviewed. This review describes CYP450 substrate inhibition examples and atypical Michaelis-Menten kinetic models, and provides insight into mechanisms of these enzymes. We also reviewed 3D structure and dynamics of CYP450 with substrate binding. Outline methods for alleviating substrate inhibition in CYP450 and other enzymes, including traditional fermentation approaches and protein engineering modifications. The comprehensive analysis presented in this study lays the foundation for enhancing the catalytic efficiency of CYP450 by deregulating substrate inhibition.

Recent insights into function, structure and modification of cytochrome P450 153 a family.

Cytochrome P450 153 A (CYP153A) is a versatile enzyme that can catalyze a wide range of oxidation reactions on various substrates. This review provides a comprehensive overview of the current state of knowledge on CYP153A, including its classification, structure, function, and potential applications in biotechnology and pharmaceuticals. The CYP153A family encompasses many enzymes with different functions on a variety of substrates. We also discuss the structural features that are responsible for the different substrate specificities. Additionally, the enzyme has been engineered to increase its catalytic activity and modifications have been made to enhance its properties further. Despite its potential, challenges and limitations associated with studying and exploiting CYP153A remain, such as low expression levels and substrate inhibition. Nonetheless, ongoing research is exploring new ways to harness the enzyme's capabilities, particularly in synthetic biology, biocatalysis, and drug discovery, making it an exciting target for future research.

Key enzymes involved in the utilization of fatty acids by Saccharomyces cerevisiae: a review.

Saccharomyces cerevisiae is a eukaryotic organism with a clear genetic background and mature gene operating system; in addition, it exhibits environmental tolerance. Therefore, S. cerevisiae is one of the most commonly used organisms for the synthesis of biological chemicals. The investigation of fatty acid catabolism in S. cerevisiae is crucial for the synthesis and accumulation of fatty acids and their derivatives, with ß-oxidation being the predominant pathway responsible for fatty acid metabolism in this organism, occurring primarily within peroxisomes. The latest research has revealed distinct variations in ß-oxidation among different fatty acids, primarily attributed to substrate preferences and disparities in the metabolic regulation of key enzymes involved in the S. cerevisiae fatty acid metabolic pathway. The synthesis of lipids, on the other hand, represents another crucial metabolic pathway for fatty acids. The present paper provides a comprehensive review of recent research on the key factors influencing the efficiency of fatty acid utilization, encompassing ß-oxidation and lipid synthesis pathways. Additionally, we discuss various approaches for modifying ß-oxidation to enhance the synthesis of fatty acids and their derivatives in S. cerevisiae, aiming to offer theoretical support and serve as a valuable reference for future studies.