Structural phylogenomics uncovers the early and concurrent origins of cysteine biosynthesis and iron-sulfur proteins

Abstract

¹ Cysteine (Cys) has unique chemical properties of catalysis, metal chelation, and protein stabilization. While Cys biosynthesis is assumed to be very ancient, the actual time of origin of these metabolic pathways remains unknown. Here, we use the molecular clocks of protein folds and fold superfamilies to time the origin of Cys biosynthesis. We find that the tRNA-dependent biosynthetic pathway appeared ∼3.5 billion years ago while the tRNA-independent counterpart emerged ∼500 million years later. A deep analysis of the origins of Cys biosynthesis in the context of emerging biochemistry uncovers some intriguing features of the planetary environment of early Earth. Results suggest that iron-sulfur (Fe-S) proteins that use cysteinyl sulfur to bind iron atoms were not the first to arise in evolution. Instead, their origin coincides with the appearance of the first Cys biosynthetic pathway. It is therefore likely that Cys did not play an important role in the make up of primordial protein molecules and that Fe-S clusters were not part of active sites at the beginning of biological history.

¹Current address: Biochemical Engineering Institute, Saarland University, Campus A 1.5, 66123 Saarbrücken, Germany

Keywords:

• cysteine biosynthesis
• molecular clock
• protein structure
• iron-sulfur proteins
• evolution

Acknowledgments

We are grateful to Dr Feng-Qin Ji and Ms Guang-Yan Tang for their helpful assistance. This work was supported by the National Basic Research Program of China (973 project, grants 2012CB721000 and 2010CB126100), the National Natural Science Foundation of China (grant 21173092), the Fundamental Research Funds for the Central Universities (grants 2011PY142 and 2011PY027) (all to HYZ) and by the National Science Foundation (grant MCB-0749836) (to GCA).

Notes

¹Current address: Biochemical Engineering Institute, Saarland University, Campus A 1.5, 66123 Saarbrücken, Germany