公开(公告)号：US09458479B2

公开(公告)日：2016-10-04

申请号：US14860103

申请日：2015-09-21

申请人： THE JOHNS HOPKINS UNIVERSITY

发明人： Craig Arthur Townsend ,  Micah Jeffrey Bodner ,  Ryan Martin Phelan ,  Michael Francis Freeman

IPC分类号： C07D477/20 ,  C12P17/10 ,  C12P17/18

CPC分类号： C12P17/10 ,  C07D477/20 ,  C12P17/184

摘要： The presently disclosed subject matter demonstrates that ThnG and ThnQ enzymes encoded by the thienamycin gene cluster in Streptomyces cattleya oxidize the C-2 and C-6 moieties of carbapenems, respectively. ThnQ stereospecifically hydroxylates PS-5 giving N-acetyl thienamycin. ThnG catalyzes sequential desaturation and sulfoxidation of PS-5, giving PS-7 and its sulfoxide. The ThnG and ThnQ enzymes are relatively substrate selective, but give rise to the oxidative diversity of carbapenems produced by S. cattleya, and orthologues likely function similarly in allied streptomyces.

摘要翻译： 目前公开的主题表明，由链霉菌链霉菌中的噻吩霉素基因簇编码的ThnG和ThnQ酶分别氧化碳青霉烯的C-2和C-6部分。 ThnQ立体选择性羟基化PS-5给予N-乙酰基噻吩霉素。 ThnG催化PS-5的顺序去饱和和亚磺氧化，得到PS-7及其亚砜。 ThnG和ThnQ酶是相对底物选择性的，但导致由S. cattleya产生的碳青霉烯类的氧化多样性，直系同源物在相关的链霉菌中可能具有相似的功能。