Streptomyces cytochromes P450: applications in drug metabolism

Author： Lamb David C Waterman Michael R Zhao Bin

ISSN： 1742-5255

Source： Expert Opinion on Drug Metabolism and Toxicology, Vol.9, Iss.10, 2013-10, pp. : 1279-1294

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Abstract

Introduction: The biotransformation of drugs is critical in assessing safety and efficacy prior to human use. Cytochrome P450 (CYP; P450) enzymes are major enzymes involved in drug metabolism and bioactivation. In general, animal model systems are widely used to evaluate drug candidate toxicity and metabolism. Streptomyces strains have also been used for the metabolism of drugs screening prior to use in human medicine. Areas covered: Utilizing Streptomyces P450s uncovered by genomics to generate drug metabolites represents an additional practical means of new drug screening approach. Now, in the first such review since the advent of the post-genomic era, the authors provide an update on the present knowledge concerning the application of the Streptomyces species and associated P450s with their role(s) in drug metabolism. Expert opinion: Currently traditional biochemical methodology, such as chemical screening to identify substrates using purified enzymes, is still required for successful drug development. Nevertheless, the ability of the Streptomyces species, and their associated P450 enzymes, has shown promise for drug development because of their ability to mimic human drug-metabolizing P450. Furthermore, it should be pointed out that the metabolism of drug candidates with Streptomyces P450 may present a generation of novel products with totally different pharmacology with improved efficacy and pharmacokinetic profile.