2019 ; Vol.29-3: 367~372
|Author||Nguyen Lan Huong, Na Joon Lee, Hyun Ha Hwang, Hye Bin Son, Hye Ji Kim, Eun Gyo Seo, Nguyen Huu Hoang, Je Won Park|
|Place of duty||Department of Biotechnology Convergent Pharmaceutical Engineering, SunMoon University|
|Title||In Vivo Characterization of Phosphotransferase-Encoding Genes istP and forP as Interchangeable Launchers of the C3’,4’-Dideoxygenation Biosynthetic Pathway of 1,4-Diaminocyclitol Antibiotics|
J. Microbiol. Biotechnol.2019 ;
|Abstract||Deactivation of aminoglycosides by their modifying enzymes, including a number of
aminoglycoside O-phosphotransferases, is the most ubiquitous resistance mechanism in
aminoglycoside-resistant pathogens. Nonetheless, in a couple of biosynthetic pathways for
gentamicins, fortimicins, and istamycins, phosphorylation of aminoglycosides seems to be a
unique and initial step for the creation of a natural defensive structural feature such as a 3’,4’-
dideoxy scaffold. Our aim was to elucidate the biochemical details on the beginning of these
C3’,4’-dideoxygenation biosynthetic steps for aminoglycosides. The biosynthesis of istamycins
must surely involve these 3’,4’-didehydroxylation steps, but much less has been reported in
terms of characterization of istamycin biosynthetic genes, especially about the
phosphotransferase-encoding gene. In the disruption and complementation experiments
pointing to a putative gene, istP, in the genome of wild-type Streptomyces tenjimariensis, the
function of the istP gene was proved here to be a phosphotransferase. Next, an in-frame
deletion of a known phosphotransferase-encoding gene forP from the genome of wild-type
Micromonospora olivasterospora resulted in the appearance of a hitherto unidentified fortimicin
shunt product, namely 3-O-methyl-FOR-KK1, whereas complementation of forP restored the
natural fortimicin metabolite profiles. The bilateral complementation of an istP gene (or forP)
in the ΔforP mutant ( or ΔistP mutant strain) successfully restored the biosynthesis of 3’,4’-
dideoxy fortimicins and istamycins , thus clearly indicating that they are interchangeable
launchers of the biosynthesis of 3’,4’-dideoxy types of 1,4-diaminocyclitol antibiotics.|
|Key_word||Aminoglycoside, istamycin, fortimicin, istP, 1-O-methyl-FOR-KK1|
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