Vitenskapelig artikkel

Total biosynthesis of the cyclic AMP booster forskolin from Coleus forskohlii

Pateraki, Irini; Andersen-Ranberg, Johan; Jensen, Niels Bjerg; Wubshet, Sileshi Gizachew; Heskes, Allison Maree; Forman, Victor; Hallström, Björn M.; Hamberger, Britta; Motawia, Mohammed Saddik; Olsen, Carl Erik; Staerk, Dan; Hansen, Jørgen; Møller, Birger Lindberg; Hamberger, Björn

Publikasjonsdetaljer

Tidsskrift: eLIFE, vol. 6, 2017

Internasjonale standardnumre:
Trykt: 2050-084X
Elektronisk: 2050-084X

Open Access: gold

Lenker:
ARKIV
DOI

Forskolin is a unique structurally complex labdane-type diterpenoid used in the
treatment of glaucoma and heart failure based on its activity as a cyclic AMP booster. Commercial
production of forskolin relies exclusively on extraction from its only known natural source, the plant
Coleus forskohlii, in which forskolin accumulates in the root cork. Here, we report the discovery of
five cytochrome P450s and two acetyltransferases which catalyze a cascade of reactions converting
the forskolin precursor 13R-manoyl oxide into forskolin and a diverse array of additional labdane-
type diterpenoids. A minimal set of three P450s in combination with a single acetyl transferase was
identified that catalyzes the conversion of 13R-manoyl oxide into forskolin as demonstrated by
transient expression in Nicotiana benthamiana. The entire pathway for forskolin production from
glucose encompassing expression of nine genes was stably integrated into Saccharomyces
cerevisiae and afforded forskolin titers of 40 mg/L.