title: Influence of ancillary genes, encoding aspects of methionine metabolism, on tylosin biosynthesis in Streptomyces fradiae.
abstract: The tylosin-biosynthetic (tyl) gene cluster of Streptomyces fradiae contains ancillary genes that encode functions normally associated with primary metabolism. These can be disrupted without loss of viability, since equivalent genes (presumably used for 'housekeeping' purposes) are also present elsewhere in the genome. The tyl cluster also contains two genes that encode products unlike any proteins in the databases. Two ancillary genes, metF (encoding N5,N10-methylenetetrahydrofolate reductase) and metK, encoding S-adenosylmethionine synthase, flank one of the 'unknown' genes (orf9) in the tyl cluster. In a strain of S. fradiae in which all three of these genes were disrupted, tylosin production was reduced, although this effect was obscured in media supplemented with glycine betaine which can donate methyl groups to the tetrahydrofolate pool. Apparently, one consequence of the recruitment of ancillary genes into the tyl cluster is enhanced capacity for transmethylation during secondary metabolism.
authors.affiliation: Department of Biochemistry, University of Leicester, UK.
authors.forename: A R
authors.initials: AR
authors.lastname: Butler
authors.forename: A R
authors.initials: AR
authors.lastname: Gandecha
authors.forename: E
authors.initials: E
authors.lastname: Cundliffe
mesh_terms: D000595:Amino Acid Sequence; D017124:Conserved Sequence; D004269:DNA, Bacterial / Q000737:chemistry; D004352:Drug Resistance, Microbial / Q000235:genetics; D005285:Fermentation; D005798:Genes, Bacterial; D008715:Methionine / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D005810:Multigene Family; D015183:Restriction Mapping; D017422:Sequence Analysis, DNA; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism; D015645:Tylosin / Q000096:biosynthesis*
chemical_list: D004269:DNA, Bacterial; D008715:Methionine; D015645:Tylosin