A two-vector system for the production of recombinant polyketides in Streptomyces

A two-vector system was developed for heterologous expression of the three genes comprising the 6-deoxyerythronolide B synthase (DEBS) polyketide gene cluster. Individual DEBS genes and pairwise combinations of two such genes were each cloned downstream of the actinorhodin (actI) promoter in two com patible Streptomyces vectors: the autonomously replicating vector, pKAO127' Kan', and the integrating vector, pSET152, The resulting plasmids were eith er simultaneously or sequentially transformed into Streptomyces lividans K4 -114. Efficient trans-complementation of modular polyketide synthase subuni t proteins occurred when the respective genes were transcribed from the two vectors and resulted in production of the erythromycin precursor 6-deoxyer ythronolide B (6-dEB).