A gene cluster for the mevalonate pathway from Streptomyces sp strain CL190

A biosynthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1.1.1.34 ), the rate-limiting enzyme of the mevalonate pathway for isopentenyl dipho sphate biosynthesis, had previously been purified from Streptomyces sp. str ain CL190 and its corresponding gene (hmgr) had been cloned (S. Takahashi, T. Kuzuyama, and H. Seto, J. Bacteriol. 181:1256-1263, 1999). Sequence anal ysis of the flanking regions of the hmgr gene revealed five new open readin g frames, orfA to -E, which showed similarity to those encoding eucaryotic and archae bacterial enzymes for the mevalonate pathway. Feeding experiment s with [1-C-13]acetate demonstrated that Escherichia coli JM109 harboring t he hmgr gene and these open reading frames used the mevalonate pathway unde r induction with isopropyl beta-D-thiogalactopyranoside. This transformant could grow in the presence of fosmidomycin, a potent and specific inhibitor of the nonmevalonate pathway, indicating that the mevalonate pathway, intr insically absent in E. coli, is operating in the E. coli transformant. The hmgr gene and orfABCDE are thus unambiguously shown to be responsible for t he mevalonate pathway and to form a gene cluster in the genome of Streptomy ces sp. strain CL190.