title: Direct fermentative production of acyltylosins by genetically-engineered strains of Streptomyces fradiae.
abstract: A tylosin-producer, Streptomyces fradiae, was transformed with plasmids carrying genes from Streptomyces thermotolerans that are involved in acyl modification of macrolide antibiotics. A transformant with pMAB3, in which macrolide 4"-O-acyltransferase gene (acyB1) and its regulatory gene (acyB2) are subcloned, produced several types of 4"-O-acyltylosins. A transformant with pAB11 delta EH containing macrolide 3-O-acyltransferase gene (acyA) in addition to the above two genes produced 3-O-acetyltylosin and 3-O-acetyl-4"-O-acyltylosins. Among the products of the latter transformant, 3-O-acetyl-4"-O-isovaleryltylosin (AIV) was detected as a minor component. When L-leucine, a precursor of isovaleryl-CoA, was added to the medium at the late stage of the fermentation, AIV content among the total macrolides increased ten-fold and AIV became a main product. This fact suggests that a high level of endogenous isovaleryl-CoA may be essential for the selective production of AIV by S. fradiae carrying pAB11 delta EH.
authors.affiliation: Merican Corporation, Central Research Laboratories, Kanagawa, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Arisawa
authors.forename: N
authors.initials: N
authors.lastname: Kawamura
authors.forename: T
authors.initials: T
authors.lastname: Narita
authors.forename: I
authors.initials: I
authors.lastname: Kojima
authors.forename: K
authors.initials: K
authors.lastname: Okamura
authors.forename: H
authors.initials: H
authors.lastname: Tsunekawa
authors.forename: T
authors.initials: T
authors.lastname: Yoshioka
authors.forename: R
authors.initials: R
authors.lastname: Okamoto
mesh_terms: D000215:Acylation; D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D005285:Fermentation; D007218:Industrial Microbiology / Q000379:methods; D010957:Plasmids / Q000737:chemistry / Q000235:genetics; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D014170:Transformation, Genetic; D015645:Tylosin / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C085543:acyB2 protein, Streptomyces thermotolerans; C031783:3-acetyl-4''-isovaleryltylosin; D000217:Acyltransferases; C085542:4''-mycarosyl isovaleryl-coenzyme A transferase; D015645:Tylosin