Moreno Charles M, Moreno Jaclyn N, Valdez Matthew C, Baldwin Melinda P, Vallor Ana C, Carvalho Paulo B
Department of Pharmaceutical Sciences, Feik School of Pharmacy, University of the Incarnate Word, San Antonio, TX 78212, USA.
Department of Biology, School of Mathematics, Science, and Engineering, University of the Incarnate Word, San Antonio, TX 78209, USA.
Metabolites. 2024 Feb 1;14(2):101. doi: 10.3390/metabo14020101.
The synthetic cytokinin forchlorfenuron (FCF), while seemingly presenting relatively low toxicity for mammalian organisms, has been the subject of renewed scrutiny in the past few years due to its increasing use in fruit crops and potential for bioaccumulation. Despite many toxicological properties of FCF being known, little research has been conducted on the toxicological effects of its secondary metabolites. Given this critical gap in the existing literature, understanding the formation of relevant FCF secondary metabolites and their association with mammalian metabolism is essential. To investigate the formation of FCF metabolites in sufficient quantities for toxicological studies, a panel of four fungi were screened for their ability to catalyze the biotransformation of FCF. Of the organisms screened, (ATCC 9245), a filamentous fungus, was found to convert FCF to 4-hydroxyphenyl-forchlorfenuron, the major FCF secondary metabolite identified in mammals, after 26 days. Following the optimization of biotransformation conditions using a solid support system, media screening, and inoculation with a solid pre-formed fungal mass of , this conversion time was significantly reduced to 7 days-representing a 73% reduction in total reaction time as deduced from the biotransformation products and confirmed by LC-MS, NMR spectroscopic data, as well as a comparison with synthetically prepared metabolites. Our study provides the first report of the metabolism of FCF by . These findings suggest that can produce FCF secondary metabolites consistent with those produced via mammalian metabolism and could be used as a more efficient, cost-effective, and ethical alternative for producing those metabolites in useful quantities for toxicological studies.
合成细胞分裂素氯吡脲(FCF)虽然对哺乳动物机体似乎毒性相对较低,但由于其在水果作物中的使用日益增加以及具有生物累积的可能性,在过去几年中一直受到重新审视。尽管FCF的许多毒理学特性已为人所知,但关于其二级代谢产物的毒理学效应的研究却很少。鉴于现有文献中的这一关键空白,了解相关FCF二级代谢产物的形成及其与哺乳动物代谢的关联至关重要。为了研究足够数量的FCF代谢产物以用于毒理学研究,筛选了一组四种真菌催化FCF生物转化的能力。在所筛选的生物体中,丝状真菌(ATCC 9245)在26天后被发现可将FCF转化为4-羟基苯基氯吡脲,这是在哺乳动物中鉴定出的主要FCF二级代谢产物。在使用固体支持系统、培养基筛选以及接种固体预形成的真菌团块优化生物转化条件后,这种转化时间显著缩短至7天,从生物转化产物推断并经液相色谱 - 质谱联用(LC-MS)、核磁共振(NMR)光谱数据以及与合成制备的代谢产物比较证实,总反应时间减少了73%。我们的研究首次报道了(ATCC 9245)对FCF的代谢。这些发现表明,(ATCC 9245)可以产生与通过哺乳动物代谢产生的FCF二级代谢产物一致的产物,并且可以用作一种更高效、更具成本效益且符合伦理的替代方法,用于生产足够数量的这些代谢产物以进行毒理学研究。