Abourashed E A, Clark A M, Hufford C D
Department of Pharmacognosy and National Center for the Development of Natural Products, Research Institute for Pharmaceutical Sciences, The University of Mississippi, University, MS 38677, USA.
Curr Med Chem. 1999 May;6(5):359-74.
The utilization of microbes as models for mammalian metabolism of xenobiotics has been well established since the concept was first introduced by Smith and Rosazza in the early seventies. The core assumption of this concept rests on the fact that fungi are eukaryotic organisms that possess metabolizing enzyme systems similar to those present in mammalian systems. Hence, the outcome of xenobiotic metabolism in both systems is expected to be similar, if not identical, and, thus, fungi can be used to predict the outcome of mammalian metabolism of various xenobiotics, including drugs. Utilizing microbial models offers a number of advantages over the use of animals in metabolism studies, mainly reduction in use of animals, ease of setup and manipulation, higher yield and diversity of metabolite production, and lower cost of production. In a continuation to our contribution to this field, this review will outline the results of studies that were conducted over the last seven years to emphasize the similarities between the microbial and mammalian metabolic pathways of xenobiotics through the endorsement of the concept of microbial models of mammalian metabolism .
自七十年代初史密斯和罗萨扎首次提出微生物可作为哺乳动物对外源化合物代谢的模型这一概念以来,该模型的应用已得到充分确立。这一概念的核心假设基于这样一个事实,即真菌是真核生物,拥有与哺乳动物系统中相似的代谢酶系统。因此,预计这两个系统中对外源化合物代谢的结果即使不完全相同也会相似,从而真菌可用于预测包括药物在内的各种外源化合物在哺乳动物体内的代谢结果。与在代谢研究中使用动物相比,利用微生物模型具有许多优势,主要包括减少动物使用、易于设置和操作、代谢产物产量更高且种类更多以及生产成本更低。作为我们对该领域贡献的延续,本综述将概述过去七年所开展研究的结果,通过认可哺乳动物代谢的微生物模型概念来强调微生物和哺乳动物对外源化合物代谢途径之间的相似性。