Post Doc (Phd graduate)
Harvesting Anti-Cancer Compounds
Did you know that some plants form compounds with anti-cancer effects when they need to defend themselves? Johan Andersen-Ranberg is trying to trick the recipes for these compounds out of the plants, as to create new cheap ways of producing otherwise very expensive medicines. In this way, cancer treatment with these effective but rare compounds can be made available for widespread use.
What is your project about?
I am trying to find out how plants synthesize a class of very useful compounds called diterpenoids. The first part of the diterpenoid biosynthesis has been mapped out. It comprises the assembly of the 20-carbon atom backbone that all molecules belonging to the terpenoid class share. I am focusing on the second part of the synthesis, where the specialized group of enzymes called cytochrome P450s (CYPs) decorate the terpenoid backbone with various side chains and active groups in a region- and stereo specific manner, creating a diverse set of molecules with many different physiological roles. Plant cells use some of these as defense compounds, which often have medicinal effects in humans.F
Figure: The combinatorial wheel - symbolizes how combinations of diTPS from different plant species can be used for expanding the diversity of diterpene compounds derived from geranylgeranyl pyrophosphate (GGPP, shown in the center of the figure).
I am working on a new approach to identify novel drug candidates, by expressing various P450 enzymes that create analogs or derivates of known drug candidates. Furthermore I am working on sequencing the transcriptome of the tissue from where the diterpenoids of interest originate, to map which P450 enzymes play a role in their biosynthesis. I am planning homology studies with related well-described P450s in the specialized metabolism and evolutionary mapping of subfamilies within the P450 enzyme class. In parallel I will attempt to identify substrate and product of the target enzymes using E.coliand in vitro assays. In concert, this research will hopefully bring us closer to an understanding of how different terpenoids are synthesized and how we can use them.
How do you see your work being applied outside the world of research?
But the fruits of my research are also planned to be used in the light driven project, which aims at establishing photosynthetic production of high-value compounds, such as terpenoids with anti-cancer properties. One of the goals is to insert the biosynthetic pathways into chloroplasts to optimize the product output.
What motivates you in your work?
It motivates me to analyze the data, and thereby adding pieces to the metabolic puzzle that we are studying in our group. I also enjoy the interaction with the other investigators, both my collaborators within and outside the department.
Why did you choose to work with Synthetic Biology?
I think that the strength of being a part of a multidisciplinary research center such as Center for Synthetic Biology, is that you are surrounded by very bright people who puts a lot of energy into their work. Also the Center has resources to allow you to pursue different research ideas.
In what way do you collaborate with researchers from the other scientific disciplines? Who do you collaborate with?
Within the Center for Synthetic Biology, my project is a part of the light driven synthesis project, in which I am collaborating Professor Poul Erik Jensen, my supervisor Björn Hamberger and postdoc Agnieszka Zygadlo among others. I currently have a very strong collaboration with the company Evolva. I am also collaborating with Japanese researchers from University of Shizouka. They inspire me, and help me troubleshoot. One of them is visiting shortly. In the future, we will characterize the target enzymes in collaboration with people from Nano Science working within the Center for Synthetic Biology.
What accomplishment are you most proud of?
I am proud of having in collaboration with others, established a platform for expression of diterpene synthases with a very high success rate.
What do you do in your spare time?
I enjoy kitesurfing, singing and skiing.
Plants are the best chemists in the world
With the ability to produce complex, useful molecules out of renewable resources, harnessing their ability is a priority for everything from medicine to food production. Watch this movie made by ABSC TV about Center for Synthetic Biology feat. Johan Andersen-Ranberg among others
|Since 2014||Post Doc, Section for Plant Biochemistry, Department of Plant and Environmental Sciences, University of Copenhagen.|
|2011 - 2014||PhD student, Center for Synthetic Biology, Section for Plant Biochemistry, Department of Plant and Environmental Sciences, University of Copenhagen (Supervisor: Björn Hamberger).|
|2013||Research visits at the University of Midsweden, Sweden and at the University of Shizouka, Japan (2 months).|
|2009 - 2011||MSc Applied Biotechnology, University of Uppsala, Sweden, Master thesis title: Utilizing Synthetic Biology in Cyanobacteria|
Collaborations within the Center for Synthetic Biology
Elias Englund, E., Andersen-Ranberg, J., Miao, R., Hamberger, B. and Lindberg, P. Metabolic engineering of Synechocystis sp. PCC 6803 for production of the plant diterpenoid manoyl oxide. ACS Synth. Biol., DOI: 10.1021/acssynbio.5b00070 (2015)
Pateraki, I.*, Andersen-Ranberg, J.*, Hamberger, B., Heskes. A.M., Martens, A.M., Zerbe, P., Bach, S.B., Møller, B.L., Bohlmann, J., Hamberger, B. Manoyl oxide (13R), the biosynthetic precursor of forskolin, is synthesized in specialized root cork cells in Coleus forskohlii. Plant Physiology 164(3): 1222-1236, doi: 10.1104/pp.113.228429 (2014). *authors contributed equally to this publication
Bach, S.S., Bassard, J.-E., Andersen-Ranberg, J., Møldrup, M.E., Simonsen, H.T., Hamberger, B. High-throughput testing of terpenoid biosynthesis candidate genes using transient expression in Nicotiana benthamiana. Methods Mol Biol: Plant Isoprenoids 1153: 245-255, doi: 10.1007/978-1-4939-0606-2_18 (2014).
Nielsen, M.T., Andersen-Ranberg, J., Christensen, U., Kristensen, M., Harrison, S.J., Olsen, C.E., Hamberger, B., Møller, B.L.. Microbial synthesis of the forskolin precursor manoyl oxide in enantiomerically pure form. Journal of Applied and Environmental Microbiology doi:10.1128/AEM.02301-14 (2014).