Assembly of non-natural electron transfer conduits in the cytochrome P450 system: a critical assessment and update of artificial redox constructs amenable to exploitation in biotechnological areas.
The high plasticity of the active-site cavity of cytochromes P450, permitting reactivity toward a vast array of compounds, makes these enzymes attractive targets for biotechnological application. Escalating attention in this area is driven by remarkable progress in the rational design by DNA shuffling of self-sufficient, multi-domain P450/electron donor constructs simplifying the composition of biocatalytic systems. Moreover, versatile approaches were undertaken to supersede the well-established, NAD(P)H-steered proteinaceous redox chains by cost-effective alternative electron transfer conduits constituted of organometallic mediators or photoactivatable redox triggers. Electrochemical techniques have proven particularly useful: employing different types of carbon- and metal-based electrodes for the fabrication of biosensors, the continuing challenge was to optimize the conductive properties of these devices by creating biocompatible interfaces for transferring electrons between sensor surfaces and redox proteins. The present review provides a critical update of the most significant breakthroughs in innovative manipulation of the redox machinery, giving an impulse to exploitation of P450s in fields such as the production of fine chemicals, drug processing, medicinal diagnostics and remediation of biotopes contaminated with harmful environmental pollutants.
Hlavica
Peter
P
Walther-Straub-Institut für Pharmakologie und Toxikologie der LMU, Goethestrasse 33, D-80336 München, Germany. hlavica@lrz.uni-muenchen.de
D000818:Animals; D001673:Biodegradation, Environmental; D015374:Biosensing Techniques; D055598:Chemical Phenomena; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D055664:Electrochemical Techniques; D004566:Electrodes; D004579:Electron Transport / Q000235:genetics; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D010105:Oxygenases / Q000235:genetics / Q000378:metabolism; D004364:Pharmaceutical Preparations; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000502:physiology
D004364:Pharmaceutical Preparations; D011993:Recombinant Fusion Proteins; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D010105:Oxygenases