Molybdenum cofactor biology, evolution and deficiency

The molybdenum cofactor (Moco) represents an ancient metal-sulfur cofactor, which participates as catalyst in carbon, nitrogen and sulfur cycles, both on individual and global scale. Given the diversity of biological processes dependent on Moco and their evolutionary age, Moco is traced back to the last universal common ancestor (LUCA), while Moco biosynthetic genes underwent significant changes through evolution and acquired additional functions. In this review, focused on eukaryotic Moco biology, we elucidate the benefits of gene fusions on Moco biosynthesis and beyond. While originally the gene fusions were driven by biosynthetic advantages such as coordinated expression of functionally related proteins and product/substrate channeling, they also served as origin for the development of novel functions. Today, Moco biosynthetic genes are involved in a multitude of cellular processes and loss of the according gene products result in severe disorders, both related to Moco biosynthesis and secondary enzyme functions.

Automated summary

The molybdenum cofactor (Moco) is an ancient metal-sulfur cofactor that plays a catalytic role in carbon, nitrogen, and sulfur cycles. Moco traces back to LUCA, and its biosynthetic genes have acquired additional functions through evolution, with gene fusions serving as origins for the development of novel functions. Today, Moco biosynthetic genes are involved in a multitude of cellular processes and their loss can lead to severe disorders.