Abstract

General molecular organization of living beings is determined by the flow of energy through the Earth's surface, and is characterized by a limited set of small molecules and polymers, which dominates their chemical constitution. In the 21^th century, biology, being previously dominant analytical science has reached a point of being the science of synthesis i.e. synthetic biology. In this perspective, I will argue that the utmost goal of such engineering biology is attempt to change chemical composition of the living cells i.e. to create artificial biodiversity in the frame of carbon-based life chemistry. Thereby, the main obstacle is to find an expedient route to change and expand the fundamental chemistry of life. One of the most promising approaches towards synthetic cell design is the inclusion of amino acid building blocks beyond the canonical 20 (i.e. expanding the genetic code) allowing for alternative reading of the genetic code. Thus, I will briefly elaborate the challenges as well as possible consequences of expanding the genetic code and metabolism of microbial strains for using novel bio-orthogonal chemistries recruited during the engineering process. For example, reprogramming protein biosynthesis with various noncanonical amino acids (ncAAs) will allow the development of industrial microbial strains with enhanced chemical diversity. In consequence, this would enable the creation of safe strains with novel functionalities such as a ‘genetic firewall’, which could potentially be a novel biosafety tool. Such synthetic cells characterized by orthogonal chemistries will have the potential to perform (bio)- chemical transformations currently existing under the exclusive domain of classical synthetic chemistry. In this journey, we will witness the consolidation of Xenobiology (XB), a marriage of chemical synthesis with synthetic biology, to build artificial biological systems for challenging biochemical transformations to address technological problems, while opening the door to a parallel biochemical world. Finally, I will discuss the potential impacts of XB in astrobiology and in the meaning and origin of life.

Keywords: Artificial life, astrobiology, bio-orthogonality, directed evolution, genetic code, genetic firewall, synthetic biology, synthetic cells.

Graphical Abstract