Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, New York.
Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, China.
Biotechnol Bioeng. 2018 Nov;115(11):2771-2777. doi: 10.1002/bit.26735. Epub 2018 Sep 15.
The biosynthetic flexibility associated with the antibiotic natural product erythromycin is both remarkable and utilitarian. Product formation is marked by a modular nature where directing compound variation increasingly spans both the secondary metabolite core scaffold and adorning functionalization patterns. The resulting molecular diversity allows for chemical expansion of the native compound structural space. Accordingly, associated antibiotic bioactivity is expected to expand infectious disease treatment applications. In the enclosed work, new glycosylation patterns spanning the deoxysugars d-forosamine, d-allose, l-noviose, and d-vicenisamine were engineered within the erythromycin biosynthetic system established through an Escherichia coli heterologous production platform. The resulting analogs highlight the expanded flexibility of the erythromycin biosynthetic process. In addition, the new compounds demonstrated bioactivity against multiple Gram-positive tester strains, including erythromycin-resistant Bacillus subtilis, and limited activity against a Gram-negative bacterial target.
与抗生素天然产物红霉素相关的生物合成灵活性既显著又实用。产物形成的特点是模块化，其中定向化合物变化越来越跨越次生代谢物核心支架和装饰功能化模式。由此产生的分子多样性允许对天然化合物结构空间进行化学扩展。因此，相关抗生素的生物活性有望扩大传染病治疗应用。在本研究中，通过大肠杆菌异源生产平台建立的红霉素生物合成系统，对脱氧糖 d-呋喃糖胺、d-阿洛糖、l-新戊糖和 d-威西尼胺进行了新的糖基化模式工程。所得到的类似物突出了红霉素生物合成过程的扩展灵活性。此外，这些新化合物对多种革兰氏阳性测试菌株表现出生物活性，包括对红霉素耐药的枯草芽孢杆菌，并且对革兰氏阴性细菌靶标具有有限的活性。
