Immunosuppressant mycophenolic acid biosynthesis employs a new globin-like enzyme for prenyl side chain cleavage
Acta Pharmaceutica Sinica B
;
(6): 1253-1258, 2019.
Artículo
en Inglés
| WPRIM
| ID: wpr-815854
ABSTRACT
Mycophenolic acid (MPA, ) and its derivatives are first-line immunosuppressants used in organ transplantation and for treating autoimmune diseases. Despite chemical synthetic achievements, the biosynthetic formation of a seven-carbon carboxylic acid pharmacophore side chain of , especially the processes involving the cleavage of the prenyl side chain between DHMP () and DMMPA (), remains unknown. In this work, we identified a membrane-bound prenyltransferase, PgMpaA, that transfers FPP to to yield FDHMP (). Compound undergoes the first cleavage step a new globin-like enzyme PgMpaB to form a cryptic intermediate . Heterologous expression of genes in demonstrates that the second cleavage step (from to ) of is a cluster-independent process . Our results, especially the discovery of the broad tolerance of substrates recognized by PgMpaB, set up a strategy for the formation of "pseudo-isopentenyl" natural products using fungal globin-like enzymes.
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Índice:
WPRIM (Pacífico Occidental)
Idioma:
Inglés
Revista:
Acta Pharmaceutica Sinica B
Año:
2019
Tipo del documento:
Artículo
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