Multisubstrate specificity shaped the complex evolution of the aminotransferase family across the tree of life.

Autor:	Koper K; Department of Botany, University of Wisconsin-Madison, Madison, WI 53706., Han SW; Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720.; Department of Biotechnology, Konkuk University, Chungju 27478, South Korea., Kothadia R; The US Department of Energy Joint Genome Institute, Lawrence Berkeley National Laboratory, Berkeley, CA 94720., Salamon H; The US Department of Energy Joint Genome Institute, Lawrence Berkeley National Laboratory, Berkeley, CA 94720., Yoshikuni Y; Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720.; The US Department of Energy Joint Genome Institute, Lawrence Berkeley National Laboratory, Berkeley, CA 94720.; Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720.; Center for Advanced Bioenergy and Bioproducts Innovation, Lawrence Berkeley National Laboratory, Berkeley, CA 94720.; Global Center for Food, Land, and Water Resources, Research Faculty of Agriculture, Hokkaido University, Hokkaido, Japan 060-8589.; Institute of Global Innovation Research, Tokyo University of Agriculture and Technology, Tokyo 183-8538, Japan., Maeda HA; Department of Botany, University of Wisconsin-Madison, Madison, WI 53706.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Jun 25; Vol. 121 (26), pp. e2405524121. Date of Electronic Publication: 2024 Jun 17.
DOI:	10.1073/pnas.2405524121
Abstrakt:	Aminotransferases (ATs) are an ancient enzyme family that play central roles in core nitrogen metabolism, essential to all organisms. However, many of the AT enzyme functions remain poorly defined, limiting our fundamental understanding of the nitrogen metabolic networks that exist in different organisms. Here, we traced the deep evolutionary history of the AT family by analyzing AT enzymes from 90 species spanning the tree of life (ToL). We found that each organism has maintained a relatively small and constant number of ATs. Mapping the distribution of ATs across the ToL uncovered that many essential AT reactions are carried out by taxon-specific AT enzymes due to wide-spread nonorthologous gene displacements. This complex evolutionary history explains the difficulty of homology-based AT functional prediction. Biochemical characterization of diverse aromatic ATs further revealed their broad substrate specificity, unlike other core metabolic enzymes that evolved to catalyze specific reactions today. Interestingly, however, we found that these AT enzymes that diverged over billion years share common signatures of multisubstrate specificity by employing different nonconserved active site residues. These findings illustrate that AT family enzymes had leveraged their inherent substrate promiscuity to maintain a small yet distinct set of multifunctional AT enzymes in different taxa. This evolutionary history of versatile ATs likely contributed to the establishment of robust and diverse nitrogen metabolic networks that exist throughout the ToL. The study provides a critical foundation to systematically determine diverse AT functions and underlying nitrogen metabolic networks across the ToL. Competing Interests: Competing interests statement:The authors declare no competing interest.
Databáze:	MEDLINE
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