Protein domain structure uncovers the origin of aerobic metabolism and the rise of planetary oxygen

Kyung Mo Kim, Tao Qin, Ying Ying Jiang, Ling Ling Chen, Min Xiong, Derek Caetano-Anollés, Hong Yu Zhang, Gustavo Caetano-Anollés

Research output: Contribution to journalArticlepeer-review


The origin and evolution of modern biochemistry remain a mystery despite advances in evolutionary bioinformatics. Here, we use a structural census in nearly 1,000 genomes and a molecular clock of folds to define a timeline of appearance of protein families linked to single-domain enzymes. The timeline sorts out enzymatic recruitment, validates patterns in metabolic history, and reveals that the most ancient reaction of aerobic metabolism involved the synthesis of pyridoxal 5′-phosphate or pyridoxal and appeared 2.9 Gyr ago. The oxygen source for this primordial reaction was probably Mn catalase, which appeared at the same time and could have generated oxygen as a side product of hydrogen peroxide detoxification. Finally, evolutionary analysis of transferred groups and metabolite fragments revealed that oxidized sulfur did not participate in metabolism until the rise of oxygen. The evolutionary patterns we uncover in molecules and chemistries provide strong support for the coevolution of biochemistry and geochemistry.

Original languageEnglish (US)
Pages (from-to)67-76
Number of pages10
Issue number1
StatePublished - Jan 11 2012

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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