Times brings everything to those who wait

OMG, it is true that time flies by! The little story I would like to tell starts about 40 years ago when I, for the first time, got impressed by biology as a science. I was 12 years old and in the 6th class when our teacher in school told us about the magic efficiency of living organisms, no matter if it is a bacterium, a plant, or a human being. He pointed out, that they all share a cellular architecture and a comparable metabolism allowing them for an outstanding efficiency in using the energy in their food. I should emphasize, this was at a time when windmills were just toys, I played with. However, like our teacher explained, all organisms need food to survive like a car needs gasoline to drive. But in contrast to cars, they are also capable to perform complex syntheses and processes which could not be done by any machine engineered by human beings, again at a time when fancy computers or smart phones only were pure fiction in tv shows like “Star Wars”.

Our teacher’s lesson about the efficiency of biology when converting their food into energy for life made already a pretty deep impression on me. But what really blew me away was what my teacher told us about some really special organisms that even do not need to get fed but perform a process called photosynthesis instead. Being a little boy of 12 years, I could hardly imagine how e.g., plants can breathe-in a gas human beings actually breathe-out as waste gas and how such plants harvest the sun light’s energy to convert this waste gas into sugar, leaves or even wood. Of course, I could see these plants growing everywhere, but it remained magic to me and induced the wild phantasy of a 12-year-old boy. In my mind I designed a lawn mower that does not need a cable for power supply as it would “eat” the grass that it is mowing for its energy demand. Just like a sheep but faster and somehow more focused on the actual job to be done. Although sceptical, my parents actually liked the idea but rather because of the desire not to cut the cable of our mower anymore, something what repeatedly happened to them.

Later I learned that photosynthetic organisms do not only convert the sun light’s energy into food for themselves, but as primary producers basically feed all the other organisms on our planet. And as if that would not be enough already these organisms are also the origin of the other energy sources we use for heating and lighting our homes as well as for running our economy. 40 years ago, this was all about fossil energies like gas, oil and coal and this is still the reality today. But also in the future, we might use of photosynthetic organisms for energy demanding products and processes or even for directly producing the energy sources but without the indirect route via fossil resources. It was this fundamental importance of photosynthetic organisms why I decided in 1988 for the topic of my abitur thesis being “Biomass – energy and material source of the future”. At this time written on the typewriter of my father which only could be properly used by an aggressive two-finger style which I, unfortunately, still apply today on my notebook while the keyboard suffers.

After the abitur, I was lucky enough and could start my biochemistry study at the Humboldt-University in Berlin. My favourite professors had their research fields in the areas of plant biochemistry and molecular biology of cyanobacteria, the evolutionary ancestor of every plant on earth. It is not a big surprise that I also ended up in this area after the diploma and the same counts for my wife Heike, who at this time shared both with me our interest in biology and our favourite professors. After the study, Heike and me founded our first company Cyano Biotech being a natural product-based drug discovery and development company focusing on cyanobacteria as a highly prolific but still untapped source of bioactive compounds for new medicines, but also for pesticides, cosmetic and food products. And only three years later we founded our second company Cyano Biofuels focused on genetic and metabolic engineering of cyanobacteria towards industrial strain development to produce biofuels and raw materials.

Meanwhile, this journey around the world of photosynthesis last for 40 years, induced by my teacher, supported by my professors and finally joint by the most important person in my life. The fascination for photosynthetic organisms has not changed since then, but it evolved somehow from being just overwhelmed by the fantastic morphological diversity of cyanobacteria or the artfully branched limbs of trees to a more scientific point of view. When listening to the rustling of leaves in the wind today, I also start thinking about each leave being a little photobioreactor and how the light-dark changes a fluttering leave is exposed to might increase its photosynthesis rate. Interestingly, you can observe such fluttering leaves very nicely on fast growing poplar trees. In any case, I am grateful for the opportunity to research those organisms as a company as well as within a dedicated community of academics and industries towards a sustainable economy.

This brings me to our R&D project FuturoLEAF funded by the European Union (homepage). The project is coordinated by Prof. Tekla Tammelin from the VTT Technical Research Centre of Finland Ltd. Beside two more partners from Finland, the other partners are from France, Austria and Germany and represent an interdisciplinary team of scientist working in the field of biology and material sciences. The name of the project is the program as we are aiming at the creation of artificial leaves as so called solid-state photosynthetic cell factories. Hereby, the term “solid-state” reflects the encapsulation of cyanobacterial cells of high densities inside thin-layer nanocellulose-based matrices. This approach allows for both higher photosynthesis rates because of better light utilization and significant reductions of water use and, if successfully developed, might contribute to the sustainable economy in the future.

The different product syntheses for the FuturoLEAF project have been chosen wisely and are all based on different but unique properties of photosynthetic cyanobacteria. They cover for instance the production of hydrogen as bioenergy stolen from the photosynthetic light reactions or the production of ethylene as raw material based on photosynthetic carbon fixation (bio-refinery approach). Further product syntheses based on whole-cell transformations use the overexcess of reducing power at higher light intensities for reactions catalysed by oxidoreductases (bio-catalysis approach). In this context, also the unique feature of photosynthetic oxygen production shall be exploited for oxygen-depending reactions that suffer from respective limitation in conventional production systems based on E.coli.

Not least, also the production of modified active pharmaceutical ingredients (APIs) on which our company Cyano Biotech is working on, uses unique features of cyanobacteria, namely the competitive-free uptake of actively provided amino acid substrates (as the only organics in the photoautotrophic cultivation media) as well as the high substrate tolerance of their non-ribosomal peptide synthetases that uses also modified amino acid substrates and finally produce the modified API. Applying this patented method, our current focus lays on the introduction of modified amino acids with anchor groups into the potent non-ribosomal cyanotoxins making them ready-to-conjugate as a payload to the monoclonal antibodies of antibody-dug conjugates (ADCs) for the targeted treatment of cancers. In this context, our most advanced payload class with very promising in-vitro and in-vivo proof-of-concept data represent the ready-to-conjugate microcystins.

At our project consortium meeting last week in Graz (Austria), it became clear, that the FuturoLEAF project is especially depending on the interdisciplinary approach. It makes the project not only more exiting but is a prerequisite for finding potential solutions for a green and sustainable economy. Interestingly, the interdisciplinarity is partly even reflected by the CVs of single team members which counts especially for the younger scientist. There are colleagues who understand biology and material science as they studied both. Others material scientist invented methods for monitoring biological processes or take part in travel and training programs before they decide for their specific research area. Also listening to the thoughts and ideas of the next generation researchers let me think that they already start on a different level than we did after our study. I am an optimistic person in general. However, when seeing the awareness of the problems within the whole society, the willingness among researchers to think outside the own box and to count on collaborations between different sciences and the high level of education and enthusiasm of the next generation of scientist, I believe that the mankind will be able to solve the biggest challenge we are currently face to. And it is clear to me that photosynthetic organisms will be part of those solutions. We are not there yet and not tomorrow and we still need to allocate significant resources for R&D, but the current speed of development and the dedication of scientist who much better know about the urgency than we did in the past let me believe in a final success. And who knows, if the lawn mowers of the future will still have cables or batteries 😉

The writer of the blog this time is Dr. Dan Enke, the CEO of Cyano Biotech.