Format

Send to

Choose Destination
Elife. 2017 Mar 14;6. pii: e23001. doi: 10.7554/eLife.23001.

Total biosynthesis of the cyclic AMP booster forskolin from Coleus forskohlii.

Author information

1
Plant Biochemistry Laboratory, Department of Plant and Environmental Sciences, University of Copenhagen, Copenhagen, Denmark.
2
Center for Synthetic Biology "bioSYNergy", Copenhagen, Denmark.
3
Evolva A/S, Copenhagen, Denmark.
4
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
5
Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden.

Abstract

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.

KEYWORDS:

Coleus forskohlii; biochemistry; diterpenoids biosynthesis; forskolin; pathway elucidation

PMID:
28290983
PMCID:
PMC5388535
DOI:
10.7554/eLife.23001
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center