Life as We Don’t Know It Protocell experiment during the Making_Life II workshop 2014. Photo by Erich Berger. 20 Life as We Don’t Know It 21 Alternative Biofacts – Life as we don’t (yet) know it Alternative Biofacts – Life as we don’t (yet) know it Markus Schmidt1 Dr Markus Schmidt founded BIOFACTION, a technology Abstract Nediljko Budisa assessment, science communication and art-science company in Vienna, Austria. With a background in ife as we know it, the result of more than 3.5 particularly attractive targets for xenobiology. For electronic engineering, biology and risk assessment billion years of evolution, has a remarkably example, the development of alternative nucleic he carried out environmental risk assessment and Lunique and uniform biochemistry and genet- acids (xenonucleic acids, XNAs) or permutating the public perception studies in various fields, such as ic information processing. Science is now going genetic code from its current form via systematic GM-crops, nanotechnology, converging technologies, beyond these uniform structures and therefore introduction of non-canonical amino acids are and synthetic biology. He has published over 35 peer creating new-to-nature forms of life. Here, we promising routes towards biocontained synthetic review papers and 3 edited books about the future of discuss some important (yet often neglected) con- cells. Technologies derived from these scientific life. In 2010 he helped to chart the field of xenobiology. cepts, ideas and empirical works that will essentially achievements are expected to (a) design, construct contribute to our deeper understanding of life as and evolve microbes with novel metabolic capabil- Prof. Dr Nediljko “Ned” Budisa is Chemistry Professor we know it, and open up the possibilities to under- ities; (b) produce useful chemicals and materials and holder of the Tier 1 Canada Research Chair for stand, anticipate and engineer new forms of life. In with novel characteristics; (c) propagate synthetic chemical synthetic biology at the University of Manitoba. this context, we describe the field of xenobiology eco-systems and food-chains; and (d) might assist He received his PhD degree in 1997 and has done and explain its aims to expand the natural frame- in recovering from the ongoing mass extinction. pioneering work in genetic-code engineering and most work of scaffolds, chemistries and building blocks Much needs to be understood about new-to-nature recently in chemical synthetic biology (Xenobiology). to achieve new-to-nature biodiversity. The mole- life forms, but we suggest that it will be of great His research focuses primarily on the development cules, molecular complexes and processes along the interest not only for science but also for the art-sci- of in vivo methods for introducing genetically- flow of genetic information (“central dogma”) are ence community. encoded protein modifications in individual proteins, complex protein structures and whole proteomes. Life as unity The ancient Greeks, including Aristotle, believed generated spontaneously from non-living matter, in generatio spontanea, the idea that life could but that omne vivum ex ovo, all life comes from life suddenly come into being from non-living matter (Pasteur 1922). With this matter settled for once, it on an everyday basis. Pioneering empirical exam- remained unclear of what kind of components life inations of Pasteur in the 19th century, however, is made of. In this way, Pasteur provided a solid 1 Corresponding author demonstrated that life in contemporary Earth is not experimental basis for what we know today as 22 Life as We Don’t Know It 23 Alternative Biofacts – Life as we don’t (yet) know it 2 Gly Arg inheritance, or vertical gene transfer (VGT). Since expressed (Vernadsky 1998) . Vernadsky captured CGCG Ala UA AU Pro DNA CG CU Pasteur, our knowledge about basic genetics (espe- all essential components that were described as (Ciphertext, base 4) Glu UA AG His cially on genetic code and horizontal gene trans- “Gaia Hypothesis” in the 1970s which postulates that AG G G CU Asp C C Gln fer) expanded and latest at the beginning of the 21 the chemical composition of the Earth is unique UC AG A A One-way century it becomes clear that the genetic code can compared to other planets and similar cosmic bod- GC CU Leu Val U AG be referred to as the “lingua franca” of life on earth, ies due to the life processes (Lovelock and Margulis UA U G C Leu AG G Met which enables the maintenance of universal bio- 1974). Vernadsky proposed the hypothesis that all U U C UC U A One-way chemistry (Kubyshkin, Acevedo-Rocha et al. 2018). living matter can be considered as a single entity – a Phe A AU Ile Protein UC A GA RNA This establishes the basis for the transfer of genetic (super) organism that spans the entire surface of Tyr C C Lys (Ciphertext, base 20) AG G G CU (Plain text, base 4) Term AG CU Asn information (VGT) from one to the next genera- the earth – a biosphere. It is a unique system that CU AG CU AU tion in the frame of one species or population but stores chemical energy by converting (mainly) solar Ser A G GA Thr Cys Ser also dissemination of biological novelty through radiation into mechanical, molecular and chemical Trp Arg horizontal gene transfer (HGT) between different energy. species and populations. Today, we know that Vernadsky was intuitively Ideas about the interconnectedness of life on our right: although there are species barriers in the pro- planet came e.g. from Austrian Geologist Eduard duction of offspring (VGT), there are no geographi- Suess, who coined the term “biosphere” in 1875. cal limits to HGT in all habitats where bacteria, eu- The Russian/Ukrainian geologist V.I. Vernadsky karyotes, archaea and virus particles thrive – from published a book in 1926 entitled “The Biosphere” deep-sea hydrothermal wells to Siberian permafrost Figure 1 (Left) Circular depiction of the genetic code (Kubyshkin, Acevedo-Rocha et al. 2018) (Right). “Central dogma” of molecular biology describes essentially were these ideas were intuitively anticipated and (Pawluk 2017, Reche, D’Orta et al. 2018). the unidirectional flow of genetic information in life (Crick 1970). That means, once “information” has passed into protein it cannot get out again. Information inherited as DNA is transcribed to RNA (as both are nucleic acids, consisting Chemical composition and organization of life’s unity of 4 building blocks or bases) and then translated to proteins (that consist of 20 different amino acids). While information can be directly transcribed back and forth between RNA and DNA, information flow from RNA to proteins is Scientists used a large part of the 20th century to polysaccharides), and play an important role in pro- a one-way street. In this figure the term base stands for information system on the basis of 4 or 20 building blocks, not the chemical base. In RNA and reveal that the conjecture of “The Biosphere” and teins and information storage (such as DNA). Nitro- DNA the chemical and informational term happens both to be called base. the Gaia hypothesis prove to be correct up to the gen is an essential component of amino acids that molecular level. It turned out that the basic chem- make up proteins and enzymes, some of the most ical constitution of all living organisms consists of important building blocks of life, but is also part a limited number of small molecules and polymers. of DNA and enables photosynthesis in chlorophyll. The building blocks of these molecules consist pre- Oxygen is most relevant for the energy flow and dominantly of only six atoms, summarized in the breathing. Phosphorus in combination with carbon acronym CHNOPS, which stands for Carbon, Hy- and hydrogen form lipids that include fats, oils, drogen, Nitrogen, Oxygen, Phosphorus and Sulfur. and waxes to store energy or protect the organism. Carbohydrates are molecules consisting of carbon Lipids are indispensable to cells as they make up the and hydrogen atoms that are fundamental to all life cell membrane, a thin layer of molecules that define forms on Earth as they play an essential role in all the inner and outer space of the cell. Phosphorus aspects of biology, e.g. they can store energy (e.g. is also essential in the formation of the backbone as sugar molecules), provide structural support (as 2 The book remained largely unknown until its recent English translation. 24 Life as We Don’t Know It 25 Alternative Biofacts – Life as we don’t (yet) know it structure of DNA. The final letter S stands for sulfur, as A matches with T (or U) and G with C. So no Tittensor et al. 2011) use exactly the same genetic indication that all living beings are related to one an essential component of some amino acids. encoding is necessary. Only when a text based on 4 code. The code-normativity of life of Earth, the another, in the sense that we might all share an un- While CHNOPS describes the building blocks of letters is translated to a text with 20 letters, a code is tremendous lack of diversity in interpreting genetic known last universal common ancestor (LUCA) that life on the atomic level, it is actually the molecular needed. In other words a code is the key to translate information, is overwhelmingly clear. Evolution- populated the Earth billions of years ago (Aceve- level that sustains life. There are basically four cate- an input to an output when there is more than one ary biologists consider this knowledge a strong do-Rocha, Fang et al. 2013). gories of molecules that are paramount for all living possibility to do so. Extant biology without excep- beings: proteins, linear polymers such as proteins, tion uses a system where three nucleic building and nucleic acids (e.g.