必特螺旋霉素（bitespiramycin, BT）是采用基因工程技术研制的新型大环内酯类抗生素，已完成III期临床试验，正在申报新药证书。大环内酯类抗生素的糖基与抗菌活性密切相关，对这些糖基进行改造是获得新型药物的有效途径。为应对将来细菌对BT产生耐药性，拟对BT的9位福洛氨糖进行替换，获得新糖基修饰的BT类似物。通过基因阻断和回复实验鉴定出BT生物合成基因簇中负责福洛氨糖的关键生物合成基因和糖基转移酶(GT)基因；在福洛氨糖生物合成缺陷株中导入改造后的GT基因或对底物具有宽容性的异源GT基因，再导入其它糖基的生物合成基因，鉴定出转化子中产生的新糖基化的BT类似物。carbomycin与脱福洛氨糖的BT结构相似，在其宿主菌中导入不同的GT在9位形成糖基修饰，或者利用体外酶学的方法进行改造来获得新的9位糖基化产物，测定所有新糖基化产物的抗菌和抗肿瘤活性，筛选出活性好的化合物做进一步研究。

Bitespiramycin (Bitespiramycin, BT), the new macrolide developed by genetic engineering, has been completed Phase III clinical trials, and now applying for a national new drug certificate. The sugar moieties of macrolide antibiotics are closely related to antibacterial activity, and it is an effective way to obtain new drugs by exchanging diverse types of sugar. In order to create novel glycosylated derivatives of BT to deal with bacterial resistance in the future, the forosamine at 9-position of BT was replaced by other sugars. The specific biosynthetic genes and glycosyltransferase (GT) genes responsible for forosamine biosynthesis were firstly identified from BT biosynthesis gene clustered by gene disruption and recovery experiments. The domain-swapped forosamine GT genes or other substrate-broad GT genes were introduced into the forosamine-deficient mutants with expressing various other sugar biosynthetic genes, and identifying the novel glycosylated BT derivatives from the resultant strains. As carbomycin has similar chemical structure with the forosamine-deprived BT, it can also be used as a precursor of glycosylation at 9-position by introducing different GTs in its host strain, or by in vitro enzymatic methods. The all glycosylation BT analogs were determinated for their antimicrobial and antitumor activities to screen out more potent compounds for further study.