Sijbren Otto

Systems Chemistry Stratingh Institute

Steps in Building a Minimal Form of Life

How chemistry can become biology is one of the Grand Challenges in current science. We explore experimentally how the key characteristics of life can emerge spontaneously from networks of synthetic molecules in aqueous solution. 1 Following the discovery of self- replicating molecules in such networks 1 we then focused on the integration of additional life- like characteristics. These include: (i) metabolism, 2,3 where replicators catalyze reactions producing molecules that the system needs; (ii) Darwinian evolution, 4,5 where rudimentary selection among mutant replicators takes place; (iii) compartmentalization, where the replicators mediate the formation of coacervate droplets into which the replicators spontaneously partition; (iv) compartment fission, also mediated by the internalized self- replicating molecules. With these step the prospect of synthesizing life de-novo is becoming increasingly realistic. 6,7

1. Carnall, J. M. A.; Waudby, C. A.; Belenguer, A. M.; Stuart, M. C. A.; Peyralans, J. J.-P.; Otto, S. Science 2010, 327, 1502-1506.

2. Monreal Santiago, G.; Liu, K.; Browne, W. R.; Otto, S. Nature Chem. 2020, 12, 603-607.

3. Ottelé, J.; Hussain, A. S.; Mayer, C.; Otto, S. Nature Catal. 2020, 3, 547-553.

4. K. Liu, A. Blokhuis, C. van Ewijk, A. Kiani, J. Wu, .W.H. Roos, S. Otto Nature Chem. 2024, 16, 79–88.

5. Eleveld, M.; Geiger, Y.; Wu, J.; Kiani, A.; Schaeffer, G.; Otto, S. Nature Chem. 2025, 17, 132-140.

6. Adamski, P.; Eleveld, M.; Sood, A,; Kun, A.; Szilágyi, A.; Czárán, T.; Szathmáry, E.; Otto, S. Nature Rev. Chem. 2020,4, 386–403.

7. Otto, S. Acc. Chem. Res. 2022, 55, 145-155.