Metabolic Engineering

Project

Given our broad interest in (di)terpenoid metabolism, we developed a modular metabolic engineering system that enables facile assembly of diterpenoid biosynthetic pathways in E. coli.  While we have carried out some further engineering to increase flux towards terpenoid metabolism, this is not a primary focus.  In particular, we are not interested in pursuing large-scale production of any given compound, but rather developed our system as a platform for discovery and exploration of relevant biosynthetic enzymes.  Indeed, vast majority of the results described in all our enzymatic and biosynthetic studies were made using this system.  Critically, particularly with the use of synthetic codon-optimized genes, it has been possible to functionally include not only microbial, but also plant microsomal cytochrome P450 mono-oxygenases.  This has led to multiple collaborative opportunities with other groups interested in elucidating various aspects of diterpenoid biosynthesis (including from a number of medicinal plants).  In addition, our work provides proof-of-principle studies relevant to biotechnology companies interested in microbial production of terpenoids.

 

1.   Cyr, A., Wilderman, P.R., Determan, M., Peters, R.J. (2007) “A modular approach for facile biosynthesis of labdane-related diterpenes”, J. Am. Chem. Soc., 129(21):6684-6685. PMCID: PMC2518946.

2.   Gao, W., Hillwig, M.L., Huang, L., Cui, G., Wang, X., Kong, J., Yang, B., Peters, R.J. (2009) “A functional genomics approach to tanshinone biosynthesis provides stereochemical insights”, Org. Lett., 11(22):5170-5173. PMCID: PMC2776380.

3.   Zi, J., Matsuba, Y., Hong, Y.J., Jackson, A.J., Tantillo, D.J., Pichersky, E., Peters, R.J. (2014) “Biosynthesis of lycosantalonol, a cis-prenyl derived diterpenoid”, J. Am. Chem. Soc., 136(49):16951-16953. PMCID: PMC4277783.

4.         Boutanaev, A., Moses, T., Zi, J., Nelson, D., Mugford, S., Peters, R.J., Osbourn, A. (2015) “Investigation of terpene diversification across multiple sequenced plant genomes”, Proc. Natl. Acad. Sci. U.S.A., 112(1):E81-E88. PMCID: PMC4291660.

Duration: 
2015-03-28