Studies of lincosamide formation complete the biosynthetic pathway for lincomycin A.
Proc Natl Acad Sci U S A
; 117(40): 24794-24801, 2020 10 06.
Article
in En
| MEDLINE
| ID: mdl-32958639
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-á´
-erythro-α-á´
-gluco-octose and GDP-á´
-α-á´
-lincosamide as key intermediates in the pathway. However, the enzyme-catalyzed reactions resulting in the conversion of GDP-á´
-erythro-α-á´
-gluco-octose to GDP-á´
-α-á´
-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-á´
-erythro-α-á´
-gluco-octose to GDP-á´
-α-á´
-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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Streptomyces
/
Lincomycin
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2020
Document type:
Article