Discovery of New Synthetic Routes of Amino Acids in Prebiotic Chemistry

Xiao-Tian Li; Sixuan Mi; Yuzhi Xu; Bo-Wen Li; Tong Zhu; John Z H Zhang

doi:10.1021/jacsau.4c00685

Discovery of New Synthetic Routes of Amino Acids in Prebiotic Chemistry

JACS Au. 2024 Nov 18;4(12):4757-4768. doi: 10.1021/jacsau.4c00685. eCollection 2024 Dec 23.

Authors

Xiao-Tian Li¹, Sixuan Mi², Yuzhi Xu³, Bo-Wen Li², Tong Zhu^{2

3

4}, John Z H Zhang^{1

2

3

5

6}

Affiliations

¹ Faculty of Synthetic Biology, Shenzhen University of Advanced Technology, Shenzhen 518055, China.
² Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
³ NYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai 200062, China.
⁴ Shanghai Innovation Institute, Shanghai 200003, China.
⁵ Department of Chemistry, New York University, New York, New York 10003, United States.
⁶ Collaborative Innovation Center of Extreme Optics, Shanxi University, Taiyuan 030006, Shanxi, China.

Abstract

The origin of life on Earth remains one of the most perplexing challenges in biochemistry. While numerous bottom-up experiments under prebiotic conditions have provided valuable insights into the spontaneous chemical genesis of life, there remains a significant gap in the theoretical understanding of the complex reaction processes involved. In this study, we propose a novel approach using a roto-translationally invariant potential (RTIP) formulated with pristine Cartesian coordinates to facilitate the simulation of chemical reactions. By employing RTIP pathway sampling to explore the reactivity of primitive molecules, we identified several low-energy reaction mechanisms, such as two-hydrogen-transfer hydrogenation and HCOOH-catalyzed hydration and amination. This led to the construction of a comprehensive reaction network, illustrating the synthesis pathways for glycine, serine, and alanine. Further thermodynamic analysis highlights the pivotal role of formaldimine as a key precursor in amino acid synthesis, owing to its more favorable reactivity in coupling reactions compared to the traditionally recognized hydrogen cyanide. Our study demonstrates that the RTIP methodology, coupled with a divide-and-conquer strategy, provides new insights into the simulation of complex reaction processes, offering promising applications for advancing organic design and synthesis.