Hubbard Brian K, Walsh Christopher T
Department of Biological Chemistry and Molecular Pharmacolgy, Harvard Medical School, Boston, MA 02115, USA.
Angew Chem Int Ed Engl. 2003 Feb 17;42(7):730-65. doi: 10.1002/anie.200390202.
Antibiotics are precious resources in the fight to combat bacterial infections caused by pathogenic organisms. Vancomycin is one of the antibiotics of last resort in the treatment of life-threatening infections by gram-positive bacteria. The rules by which nature assembles the glycopeptide (vancomycin) and lipoglycopeptide (teicoplanin) antibiotics are becoming elucidated and verified: first amino acids are synthesized, then joined together and cross-linked. This knowledge opens up approaches for reprogramming strategies at the level of altered monomers, swapped assembly lines, and different post-assembly tailoring enzymes.
抗生素是对抗由致病生物体引起的细菌感染的宝贵资源。万古霉素是治疗革兰氏阳性菌引起的危及生命感染的最后手段之一。自然界组装糖肽(万古霉素)和脂糖肽(替考拉宁)抗生素的规则正在得到阐明和验证:首先合成氨基酸,然后连接在一起并交联。这一知识为在改变单体、交换装配线和不同的装配后修饰酶水平上重新编程策略开辟了途径。