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Studies of lincosamide formation complete the biosynthetic pathway for lincomycin A.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America . 10/6/2020, Vol. 117 Issue 40, p1-8. 8p. - Publication Year :
- 2020
-
Abstract
- The structure of lincomycin A consists of the unusual eight-carbon thiosugar core methyllincosamide (MTL) decorated with a pendent N-methylprolinyl moiety. Previous studies on MTL biosynthesis have suggested GDP-D-erythro-a-D-gluco-octose and GDP-D-a-D-lincosamide as key intermediates in the pathway. However, the enzyme-catalyzed reactions resulting in the conversion of GDP-D-erythro-a-D-glucooctose to GDP-D-a-D-lincosamide have not yet been elucidated. Herein, a biosynthetic subpathway involving the activities of four enzymes--LmbM, LmbL, CcbZ, and CcbS (the LmbZ and LmbS equivalents in the closely related celesticetin pathway)--is reported. These enzymes catalyze the previously unknown biosynthetic steps including 6-epimerization, 6,8-dehydration, 4-epimerization, and 6-transamination that convert GDP-D-erythro- a-D-gluco-octose to GDP-D-a-D-lincosamide. Identification of these reactions completes the description of the entire lincomycin biosynthetic pathway. This work is significant since it not only resolves the missing link in octose core assembly of a thiosugar-containing natural product but also showcases the sophistication in catalytic logic of enzymes involved in carbohydrate transformations. [ABSTRACT FROM AUTHOR]
- Subjects :
- *MOIETIES (Chemistry)
*NATURAL products
*BIOSYNTHESIS
*CARBOHYDRATES
*ENZYMES
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 117
- Issue :
- 40
- Database :
- Academic Search Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 146314572