In vitro characterization of LmbK and LmbO: Identification of GDP-d-erythro-α-d-gluco-octose as a key intermediate in lincomycin a biosynthesis

Chia I. Lin, Eita Sasaki, Aoshu Zhong, Hung Wen Liu

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Lincomycin A is a clinically useful antibiotic isolated from Streptomyces lincolnensis. It contains an unusual methylmercapto-substituted octose, methylthiolincosamide (MTL). While it has been demonstrated that the C 8 backbone of MTL moiety is derived from d-fructose 6-phosphate and d-ribose 5-phosphate via a transaldol reaction catalyzed by LmbR, the subsequent enzymatic transformations leading to the MTL moiety remain elusive. Here, we report the identification of GDP-d-erythro-α-d-gluco-octose (GDP-d-α-d-octose) as a key intermediate in the MTL biosynthetic pathway. Our data show that the octose 1,8-bisphosphate intermediate is first converted to octose 1-phosphate by a phosphatase, LmbK. The subsequent conversion of the octose 1-phosphate to GDP-d-α-d-octose is catalyzed by the octose 1-phosphate guanylyltransferase, LmbO. These results provide significant insight into the lincomycin biosynthetic pathway, because the activated octose likely serves as the acceptor for the installation of the C1 sulfur appendage of MTL.

Original languageEnglish
Pages (from-to)906-909
Number of pages4
JournalJournal of the American Chemical Society
Volume136
Issue number3
DOIs
Publication statusPublished - 2014 Jan 22
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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