Isobiology: A Variational Principle for Exploring Synthetic Life

Abstract

Most developments in synthetic biology try to depart from life as we know it, attempting to create orthogonal constructions. Here, following a variational principle, I try to explore how slight changes in the buildup of cells reveal critical features of life's physics. In a first section, I suggest that we use stable isotopes of the atoms of life to see how living cells fare, beginning with life in heavy water. Subsequently, isotopes of the other main biogenic atoms are suggested as an extension of the variational principle, despite their likely very small influence on the course of biological activity. Finally, two atoms of the second row of Mendeleev's table, boron and fluorine are explored as a further extension of the principle. The use of the former is still in its infancy, whereas the latter, based on existing fluorinases, could open the door to a more general use of halogens in synthetic biology.

Intersecting Xenobiology and Neometabolism To Bring Novel Chemistries to Life

“…A complementary perspective on xenobiology has been proposed by Danchin in a recent and inspiring review. [232] Besides the incorporation of xeno-elements into biochemistry by neometabolism as discussed herein, the article proposes a role for stable CHONS isotopes, with a focus on deuterium (i. e., 2 H). The review analyzes known and potential effects of 2 H on biochemical pathways based on its physicochemical properties, together with reports on the toxicity and safety of 2 H enrichment in different species.…”

Challenges and opportunities in bringing nonbiological atoms to life with synthetic metabolism

“…In this sense, directed evolution constitutes a powerful strategy for optimizing 'promiscuous' reactions inherent to the enzyme(s) under investigation. Certain chemical transformations can be catalyzed by enzymes under specific physicochemical conditions [137], yet these activities are rather secondary and highly restrained, and their potential can be unleashed with the help of rational mutagenesis and appropriate selection schemes [138]. Such a strategy represents another powerful untapped resource for establishing the assimilation of novel chemical elements [128].…”

SynBio 2.0, a new era for synthetic life: Neglected essential functions for resilience

“…In general, with the exception of the change of hydrogen to deuterium—which has measurable but moderate effects—the changes are extremely small. They can, however, help us to understand some of the key processes that “animate” chemical biology, notably by tracking isotope enrichment in mixtures of isotopes of a given atom (Danchin, 2020). More radical changes would use atoms avoided by life but sometimes used, such as fluorine and other halogens (Alves Ferreira‐Bravo & DeStefano, 2021; Heine et al, 2018), silicon (Ikeda, 2021) or arsenic (Kabiraj et al, 2022).…”