Fosfomycin monophosphate and fosfomycin diphosphate, two inactivated fosfomycin derivatives formed by gene products of fomA and fomB from a fosfomycin producing organism Streptomyces wedmorensis.

Fig. 1. Structures of FMand FMderivatives inactivated by gene products offomA andfomB. analysis revealed the presence of six open reading frames with unknownfunctions in the sequenced fragment, in addition to the four genes necessary to FMbiosynthesis. So far studied, most antibiotic-producing Streptomyces possessed resistance genes and regulatory genes in their antibiotic production gene cluster. Antibiotic resistance genes have been cloned from various organisms using antibiotic sensitive hosts, Streptomyces lividans or Escherichia coll. We investigated the FMgene cluster to identify a gene(s) which confers FMresistance to E. coli. Deletion analysis of various fragments in the FMbiosynthetic gene cluster revealed that bothfomA andfomB, formerly called as orfA and orfB9\ respectively, and characterized as FM-resistance genes, were required for complete