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Structure, function, and engineering of enzymes in isoflavonoid biosynthesis

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Abstract

Isoflavonoids are a large group of plant natural products and play important roles in plant defense. They also possess valuable health-promoting activities with significant health benefits for animals and humans. The isoflavonoids are identified primarily in leguminous plants and are synthesized through the central phenylpropanoid pathway and the specific isoflavonoid branch pathways in legumes. Structural studies of some key enzymes in the central phenylpropanoid pathway shed light on the early stages of the (iso)flavonoid biosynthetic process. Significant impact has also been made on structural studies of enzymes in the isoflavonoid branch pathways. Structures of isoflavonoid-specific NADPH-dependent reductases revealed how the (iso)flavonoid backbones are modified by reduction reactions and how enzymes specifically recognize isoflavonoids and catalyze stereo-specific reductions. Structural studies of isoflavonoid methyltransferases and glycosyltransferases revealed how isoflavonoids are further decorated with methyl group and sugars in different methylation and glycosylation patterns that determine their bioactivities and functions. In combination with mutagenesis and biochemical studies, the detailed structural information of these enzymes provides a basis for understanding the complex biosynthetic process, enzyme catalytic mechanisms, and substrate specificities. Structure-based homology modeling facilitates the functional characterization of these large groups of biosynthetic enzymes and their homologs. Structure-based enzyme engineering is becoming a new strategy for synthesis of bioactive isoflavonoids and also facilitates plant metabolic engineering towards improvement of quality and production of crop plants.

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Acknowledgments

I thank Drs. J. Wen and H. Shao for the critical reading of the manuscript. The work described from the author and his collaborator’s laboratories was supported by a grant from the US National Science Foundation (Grant no. 0416833) and funds provided by the Samuel Roberts Noble Foundation.

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Correspondence to Xiaoqiang Wang.

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Wang, X. Structure, function, and engineering of enzymes in isoflavonoid biosynthesis. Funct Integr Genomics 11, 13–22 (2011). https://doi.org/10.1007/s10142-010-0197-9

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