Dataset Information

In vitro characterization of LmbK and LmbO: identification of GDP-D-erythro-?-D-gluco-octose as a key intermediate in lincomycin A biosynthesis.

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 C8 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-?-D-gluco-octose (GDP-D-?-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-?-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.

SUBMITTER: Lin CI

PROVIDER: S-EPMC3932030 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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In vitro characterization of LmbK and LmbO: identification of GDP-D-erythro-α-D-gluco-octose as a key intermediate in lincomycin A biosynthesis.

Lin Chia-I CI Sasaki Eita E Zhong Aoshu A Liu Hung-wen HW

Journal of the American Chemical Society 20140110 3

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 C8 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-octos ...[more]

PMID: 24380627

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Dataset Information

In vitro characterization of LmbK and LmbO: identification of GDP-D-erythro-?-D-gluco-octose as a key intermediate in lincomycin A biosynthesis.

Publications

In vitro characterization of LmbK and LmbO: identification of GDP-D-erythro-α-D-gluco-octose as a key intermediate in lincomycin A biosynthesis.

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