通过一种新型细菌rhamnosyltransferase的选择性生物合成一个rhamnosyl nosiheptide
Yali Du1, Yuan Xia1, Lingrui Wu1
1Department of Biochemistry, College of Life Sciences and Technology, China Pharmaceutical University, Nanjing, Jiangsu Province, China.
Microbial biotechnology
|January 24, 2024
概括
研究人员进行了拉姆诺西化诺西 (NOS),产生了NOS-R. 这种衍生物在小鼠中显示出更好的溶解性和MRSA保护,保持类似的体外活性,突出显示了抗生素修饰的潜力.
科学领域:
- 微生物学 微生物学
- 生物化学 生物化学
- 药物发现 药物发现 药物发现
背景情况:
- 诺西 (Nosiheptide,简称NOS) 是一种类抗生素,有可能进行修改.
- 在NOS中,3-氧氨酸的部分是化学变化的目标.
- 提高NOS溶解度和对抗耐药细菌的有效性是一个关键的挑战.
研究的目的:
- 为了在3-氧胺基位点上化诺西 (NOS).
- 为了评估产生的衍生物的特性和疗效,NOS-R.
- 为了识别和描述负责NOS拉姆诺基化酶的酶.
主要方法:
- 细菌菌株的查,以检测NOS.的区域选择性拉姆诺基化.
- 发酵和净化NOS-R衍生物的发酵和净化.
- 负责的拉姆诺西尔转移酶 (SrGT822) 的鉴定和特征.
- 在体外和体外对NOS-R对MRSA的疗效测试.
主要成果:
- 杆菌种 (Streptomyces) sp. 这种杆菌种 (Streptomyces) 是一种 147326个地区选择性地生产了NOS-R,生产率为24.6%.
- 在小鼠中,NOS-R的水溶性增加了17.6倍,并对MRSA产生保护作用.
- 鉴定和优化了rhamnosyltransferase SrGT822,在pH10.0和55°C时产生了74.9%的NOS-R.
- SrGT822显示出修改复杂分子支架的潜力.
结论:
- 通过对NOS进行米化,可以获得具有增强性质的衍生物 (NOS-R).
- SrGT822是一种高效的rhamnosyltransferase,在药物修饰中具有潜在的应用.
- 这项研究为改善抗生素特性和开发新的治疗剂提供了一种新的策略.
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