Direct fermentative production of acyltylosins by genetically-engineered strains of Streptomyces fradiae.
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.
Arisawa
A
A
Merican Corporation, Central Research Laboratories, Kanagawa, Japan.
Kawamura
N
N
Narita
T
T
Kojima
I
I
Okamura
K
K
Tsunekawa
H
H
Yoshioka
T
T
Okamoto
R
R
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*
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