한상우 (Lawrence Berkeley National Laboratory, 건국대학교)

한빛사논문

조회251

Lawrence Berkeley National Laboratory, 건국대학교

CV File 101 kb

Proc. Natl. Acad. Sci. USA, Jun 25 2024, 121 (26) | https://doi.org/10.1073/pnas.2405524121 Multisubstrate specificity shaped the complex evolution of the aminotransferase family across the tree of life

Kaan Kope^ra,1, Sang-Woo Han^b,c,1, Ramani Kothadia^d , Hugh Salamon^d,2, Yasuo Yoshikuni^{b,d,e,f,g,h,3} , and Hiroshi A. Maeda^a,3

^aDepartment of Botany, University of Wisconsin-Madison, Madison,WI 53706;

^bEnvironmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720;

^cDepartment of Biotechnology, Konkuk University, Chungju 27478, South Korea;

^dThe US Department of Energy Joint Genome Institute, Lawrence Berkeley National Laboratory, Berkeley, CA 94720;

^eBiological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley,CA 94720;

^fCenter for Advanced Bioenergy and Bioproducts Innovation, Lawrence Berkeley National Laboratory, Berkeley, CA 94720;

^gGlobal Center for Food, Land, and Water Resources, Research Faculty of Agriculture, Hokkaido University, Hokkaido, Japan 060-8589; and

^hInstitute of Global Innovation Research, Tokyo University of Agriculture and Technology, Tokyo 183-8538, Japan

¹K.K. and S.-W.H. contributed equally to this work.

²Present address: Knowledge Synthesis Inc., Berkeley,CA 94710.

³To whom correspondence may be addressed. : Yasuo Yoshikuni, Hiroshi A. Maeda

Abstract

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.

논문정보

형식Research article
게재일2024년 06월 (BRIC 등록일 2024-06-18)
연구진국내+국외 연구진
분야 생명과학 > 생물공학

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