TY - JOUR
T1 - Microbial synthesis of the forskolin precursor manoyl oxide in an enantiomerically pure form
AU - Nielsen, Morten Thrane
AU - Andersen-Ranberg, Johan
AU - Christensen, Ulla
AU - Christensen, Hanne Bjerre
AU - Harrison, Scott J.
AU - Olsen, Carl Erik
AU - Hamberger, Björn Robert
AU - Møller, Birger Lindberg
AU - Nørholm, Morten
PY - 2014
Y1 - 2014
N2 - Forskolin is a promising medicinal compound belonging to a plethora of specialized plant metabolites that constitute a rich source of bioactive high-value compounds. A major obstacle for exploitation of plant metabolites is that they often are produced in small amounts and in plants difficult to cultivate. This may result in insufficient and unreliable supply leading to fluctuating and high sales prices. Hence, substantial efforts and resources have been invested in developing sustainable and reliable supply routes based on microbial cell factories. Here, we report microbial synthesis of (13R)-manoyl oxide, a proposed intermediate in the biosynthesis of forskolin and other medically important labdane-type terpenoids. Process optimization enabled synthesis of enantiomerically pure (13R)-manoyl oxide as the sole metabolite, providing a pure compound in just two steps with a yield of 10 mg/liter. The work presented here demonstrates the value of a standardized bioengineering pipeline and the large potential of microbial cell factories as sources for sustainable synthesis of complex biochemicals.
AB - Forskolin is a promising medicinal compound belonging to a plethora of specialized plant metabolites that constitute a rich source of bioactive high-value compounds. A major obstacle for exploitation of plant metabolites is that they often are produced in small amounts and in plants difficult to cultivate. This may result in insufficient and unreliable supply leading to fluctuating and high sales prices. Hence, substantial efforts and resources have been invested in developing sustainable and reliable supply routes based on microbial cell factories. Here, we report microbial synthesis of (13R)-manoyl oxide, a proposed intermediate in the biosynthesis of forskolin and other medically important labdane-type terpenoids. Process optimization enabled synthesis of enantiomerically pure (13R)-manoyl oxide as the sole metabolite, providing a pure compound in just two steps with a yield of 10 mg/liter. The work presented here demonstrates the value of a standardized bioengineering pipeline and the large potential of microbial cell factories as sources for sustainable synthesis of complex biochemicals.
U2 - 10.1128/AEM.02301-14
DO - 10.1128/AEM.02301-14
M3 - Journal article
AN - SCOPUS:84910149985
SN - 0099-2240
VL - 80
SP - 7258
EP - 7265
JO - Applied and Environmental Microbiology
JF - Applied and Environmental Microbiology
IS - 23
ER -