A. Arisawa et al., DIRECT FERMENTATIVE PRODUCTION OF ACYLTYLOSINS BY GENETICALLY-ENGINEERED STRAINS OF STREPTOMYCES-FRADIAE, Journal of antibiotics, 49(4), 1996, pp. 349-354
A tylosin-producer, Streptomyces fradiae, was transformed with plasmid
s 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 regul
atory gene (acyB2) are subcloned, produced several types of 4 ''-O-acy
ltylosins. A transformant with pAB11 Delta EH containing macrolide 3-O
-acyltransferase gene (acyA) in addition to the above two genes produc
ed 3-O-acetyltylosin and 3-O-acetyl-4 ''-O-acyltylosins. Among the pro
ducts of the latter transformant, 3-O-acetyl-4 ''-O-isovaleryltylosin
(AIV) was detected as a minor component. When L-leucine, a precursor o
f isovaleryl-CoA, was added to the medium at the late stage of the fer
mentation, AIV content among the total macrolides increased ten-fold a
nd AIV became a main product. This fact suggests that a high level of
endogenous isovaleryl-CoA maybe essential for the selective production
of AIV by S. fradiae carrying pAB11 Delta EH.