Marsden A F, Wilkinson B, Cortés J, Dunster N J, Staunton J, Leadlay P F
Cambridge Centre for Molecular Recognition and Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK.
Science. 1998 Jan 9;279(5348):199-202. doi: 10.1126/science.279.5348.199.
The wide-specificity loading module for the avermectin-producing polyketide synthase was grafted onto the first multienzyme component (DEBS1) of the erythromycin-producing polyketide synthase in place of the normal loading module. Expression of this hybrid enzyme in the erythromycin producer Saccharopolyspora erythraea produced several novel antibiotic erythromycins derived from endogenous branched-chain acid starter units typical of natural avermectins. Because the avermectin polyketide synthase is known to accept more than 40 alternative carboxylic acids as starter units, this approach opens the way to facile production of novel analogs of antibiotic macrolides.
将用于生产阿维菌素的聚酮合酶的宽特异性装载模块嫁接到生产红霉素的聚酮合酶的第一个多酶组分（DEBS1）上，以取代正常的装载模块。在红霉素产生菌糖多孢红霉菌中表达这种杂合酶，产生了几种新型抗生素红霉素，它们源自天然阿维菌素典型的内源性支链酸起始单元。由于已知阿维菌素聚酮合酶可接受40多种替代羧酸作为起始单元，这种方法为轻松生产抗生素大环内酯类的新型类似物开辟了道路。
