An additional regulatory gene for actinorhodin production in Streptomyces lividans involves a LysR-type transcriptional regulator

The sequence of a 4.8 kbp DNA fragment adjacent to the right-hand end of th e actinorhodin biosynthetic (act) cluster downstream of actVB-orf6 from Str eptomyces coelicolor A3(2) reveals six complete open reading frames, named orf7 to orf12, The deduced amino acid sequences from orf7, orf10, and orf11 show significant similarities with the following products in the databases : a putative protein from the S. coelicolor SCP3 plasmid, LysR-type transcr iptional regulators, and proteins belonging to the family of short-chain de hydro-genases/reductases, respectively. The deduced product of orf8 reveals low similarities with several methyltransferases from different sources, w hile orf9 and orf12 products show no similarities with other known proteins . Disruptions of orf10 and orf11 genes in S. coelicolor appear to have no s ignificant effect on the production of actinorhodin, Nevertheless, disrupti on or deletion of orf10 in Streptomyces lividans causes actinorhodin overpr oduction. The introduction of extra copies of orf10 and orf11 genes in an S . coelicolor actIII mutant restores the ability to produce actinorhodin, Tr anscriptional analysis and DNA footprinting indicate that orf10 represses i ts own transcription and regulates orf11 transcription, expression of which might require the presence of an unknown inducer. No DNA target for orf10 protein was found within the act cluster.