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

Nguyen Lan Huong, Na Joon Lee, Hyun Ha Hwang, Hye Bin Son, Hye Ji Kim, Eun Gyo Seo, Nguyen Huu Hoang, Je Won Park

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)367-372
Number of pages6
JournalJournal of microbiology and biotechnology
Volume29
Issue number3
DOIs
Publication statusPublished - 2019

Keywords

  • 1-o-methyl- FOR-KK1
  • 3',4'-didehydroxylation
  • Aminoglycoside
  • Fortimicin
  • Istamycin
  • Istp

ASJC Scopus subject areas

  • Biotechnology
  • Applied Microbiology and Biotechnology

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

  • Cite this