Jiang Kai, Yan Xiaoli, Deng Zixin, Lei Chun, Qu Xudong
State Key Laboratory of Microbial Metabolism & School of Life Sciences and Biotechnology and Joint International Research Laboratory of Metabolic and Developmental Sciences, Shanghai Jiao Tong University, Shanghai 200240, China.
School of Pharmacy, Fudan University, Shanghai 201203, China.
J Nat Prod. 2022 Apr 22;85(4):943-950. doi: 10.1021/acs.jnatprod.1c01089. Epub 2022 Mar 24.
Genome mining and biocatalytic modification of chemical structures are critical methods to develop new antibiotics. In this study, eight new fasamycins (, , , and -) along with five known analogues (, , , , and ) were obtained by the overexpression of two phosphopantetheinyl transferases (PPtases) in and biocatalytic transformation with two halogenases. These new compounds displayed significant activity against and , in particular, C-29-methyl and C-2/C-22-halogen derivatives. This study increases the chemical diversity of bioactive fasamycin derivatives and provides useful halogenation tools for engineering their scaffolds.
基因组挖掘和化学结构的生物催化修饰是开发新型抗生素的关键方法。在本研究中，通过在大肠杆菌中过表达两种磷酸泛酰巯基乙胺基转移酶（PPtases）并利用两种卤化酶进行生物催化转化，获得了8种新的法沙霉素（、、、和-）以及5种已知类似物（、、、、和）。这些新化合物对金黄色葡萄球菌和大肠杆菌显示出显著活性，特别是C-29-甲基和C-2/C-22-卤代衍生物。本研究增加了生物活性法沙霉素衍生物的化学多样性，并为其支架工程提供了有用的卤化工具。
