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首页> 外文期刊>Applied Microbiology >The Sterol Carrier Hydroxypropyl-β-Cyclodextrin Enhances the Metabolism of Phytosterols by Mycobacterium neoaurum
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The Sterol Carrier Hydroxypropyl-β-Cyclodextrin Enhances the Metabolism of Phytosterols by Mycobacterium neoaurum

机译：甾醇载体羟丙基-β-环糊精增强了新牙酮的植物肽酚的代谢

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摘要

Androst-4-ene-3,17-dione (AD) and androst-1,4-diene-3,17-dione (ADD) are valuable steroid pharmaceutical intermediates obtained by soybean phytosterol biotransformation by Mycobacterium . Cyclodextrins (CDs) are generally believed to be carriers for phytosterol delivery and can improve the production of AD and ADD due to their effects on steroid solubilization and alteration in cell wall permeability for steroids. To better understand the mechanisms of CD promotion, we performed proteomic quantification of the effects of hydroxypropyl-β-CD (HP-β-CD) on phytosterol metabolism in Mycobacterium neoaurum TCCC 11978 C2. Perturbations are observed in steroid catabolism and glucose metabolism by adding HP-β-CD in a phytosterol bioconversion system. AD and ADD, as metabolic products of phytosterol, are toxic to cells, with inhibited cell growth and biocatalytic activity. Treatment of mycobacteria with HP-β-CD relieves the inhibitory effect of AD(D) on the electron transfer chain and cell growth. These results demonstrate the positive relationship between HP-β-CD and phytosterol metabolism and give insight into the complex functions of CDs as mediators of the regulation of sterol metabolism.IMPORTANCE Phytosterols from soybean are low-cost by-products of soybean oil production and, owing to their good bioavailability in mycobacteria, are preferred as the substrates for steroid drug production via biotransformation by Mycobacterium . However, the low level of production of steroid hormone drugs due to the low aqueous solubility (below 0.1?mmol/liter) of phytosterols limits the commercial use of sterol-transformed strains. To improve the bioconversion of steroids, cyclodextrins (CDs) are generally used as an effective carrier for the delivery of hydrophobic steroids to the bacterium. CDs improve the biotransformation of steroids due to their effects on steroid solubilization and alterations in cell wall permeability for steroids. However, studies have rarely reported the effects of CDs on cell metabolic pathways related to sterols. In this study, the effects of hydroxypropyl-β-CD (HP-β-CD) on the expression of enzymes related to steroid catabolic pathways in Mycobacterium neoaurum were systematically investigated. These findings will improve our understanding of the complex functions of CDs in the regulation of sterol metabolism and guide the application of CDs to sterol production.
机译：Androst-4-Ene-3,17-Dione（Ad）和Androst-1,4-二烯-3,17-Dione（Add）是通过分枝杆菌大豆植物植物生物转化获得的有价值的类固醇药物中间体。通常认为环糊精（CDS）是植物甾醇递送的载体，并且可以改善AD的产生，并由于它们对类固醇溶解和类固醇细胞壁渗透性的改变而添加。为了更好地理解CD促进的机制，我们对羟丙基-β-CD（HP-β-CD）对新牙杆菌TCCC 11978 C2的植物甾醇代谢作用进行了蛋白质组学定量。通过在植物甾醇生物转化系统中添加HP-β-CD，在类固醇分解代谢和葡萄糖代谢中观察到扰动。作为植物甾醇的代谢产物，对细胞毒性和生物催化活性的广告和添加。 HP-β-CD治疗分枝杆菌缓解AD（D）对电子转移链和细胞生长的抑制作用。这些结果证明了HP-β-CD和植物甾醇代谢之间的阳性关系，并欣赏CDS的复杂功能作为甾醇代谢调节的介质。来自大豆的植物甾醇是豆油生产的低成本副产品，由于其在分枝杆菌中的良好生物利用度，作为通过分枝杆菌的生物转化的类固醇药物生产的基材是优选的。然而，由于低水溶性（低于0.1≤mmol/升）的植物甾醇而导致的类固醇激素药物的低水平限制了甾醇转化菌株的商业用途。为了改善类固醇的生物转化，环糊精（CDS）通常用作用于将疏水类固醇输送到细菌的有效载体。 CDS提高了类固醇的生物转化，因为它们对类固醇溶解和类固醇细胞壁渗透性的改变。然而，研究很少报告CD对与甾醇相关的细胞代谢途径的影响。在该研究中，系统地研究了羟丙基-β-CD（HP-β-CD）对新牙毛分泌性分解代谢途径的表达的影响。这些调查结果将改善我们对CDS在甾醇新陈代谢调节中的复杂功能的理解，并指导CD在甾醇生产中的应用。

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