Molecular cloning and analysis of a pleiotropic regulatory gene locus fromthe nystatin producer Streptomyces noursei ATCC11455

A regulatory gene locus from Streptomyces noursei ATCC14455, the producer o f the antifungal antibiotic nystatin, was cloned in Streptomyces lividans b ased on its ability to activate actinorhodin (Act) production in this host. Deletion and DNA sequencing analyses showed that a small gene, designated ssmA, located downstream of an afsR homologue (a known pleiotropic regulato r) was responsible for the Act overproduction in S. lividans. Database sear ches for the ssmA gene product revealed its limited similarity to the AfsR2 regulatory protein from S. lividans and CREA catabolite repressor from Asp ergillus nidulans. To study the effect of ssmA on nystatin production, this gene was either deleted from S. noursei genome, or placed under control of P-ermE* promoter and introduced in S. noursei. The properties of the corre sponding strains indicate that ssmA is involved in regulation of growth and antibiotic production only in the media with certain carbon sources. (C) 1 999 Published by Elsevier Science B.V. All rights reserved.