title: Characterization of mutations in regulatory genes of Tyl cluster leading to overexpression of tylosin in mutant γ-1 of Streptomyces fradiae NRRL-2702.
abstract: Tylosin is a veterinary antibiotic and is commercially produced using Streptomyces fradiae. Previously, we developed a mutant γ-1 of S. fradiae NRRL-2702 with a 6.87-fold increase in tylosin yield as compared with the wild-type strain through irradiation mutagenesis. The present studies were conducted to explore mutational changes in regulatory genes (TylQ, TylP, TylS, TylR, and TylT) of Tyl cluster that may lead to an enhanced expression of tylosin. Expression analysis by RT-PCR revealed that TylQ was switched off earlier in mutant γ-1 while no change in expression pattern of TylP was observed between the wild-type and mutant γ-1 strains. However, a point mutation with a substitution of T to A was recorded at position 214 in the 420-bp product of TylP from mutant γ-1 that resulted in a change of one amino acid (serine to threonine) at position 72. Moreover, no mutation in the nucleotide sequence of TylS, TylR, and TylT genes was detected.
authors.affiliation: Industrial Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE), P.O. Box 577, Jhang Road, Faisalabad, Pakistan, skhaliq@nibge.org.
authors.forename: Shazia
authors.initials: S
authors.lastname: Khaliq
authors.forename: Muhammad A
authors.initials: MA
authors.lastname: Ghauri
authors.forename: Kalsoom
authors.initials: K
authors.lastname: Akhtar
mesh_terms: D019943:Amino Acid Substitution; D053898:Biosynthetic Pathways / Q000235:genetics*; D004252:DNA Mutational Analysis; D020869:Gene Expression Profiling; D005809:Genes, Regulator; D005810:Multigene Family; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism*; D015645:Tylosin / Q000096:biosynthesis*
chemical_list: D015645:Tylosin