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Proc Natl Acad Sci U S A

Title:		Structural basis for divergent and convergent evolution of catalytic machineries in plant aromatic amino acid decarboxylase proteins
Author(s):		Torrens-Spence MP; Chiang YC; Smith T; Vicent MA; Wang Y; Weng JK;
Address:		"Whitehead Institute for Biomedical Research, Cambridge, MA 02142. Department of Physics, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139. Department of Biology, Williams College, Williamstown, MA 01267. Whitehead Institute for Biomedical Research, Cambridge, MA 02142; wengj@wi.mit.edu"
Journal Title:		Proc Natl Acad Sci U S A
Year:		2020
Volume:		20200505
Issue:		20
Page Number:		10806 - 10817
DOI:		10.1073/pnas.1920097117
ISSN/ISBN:		1091-6490 (Electronic) 0027-8424 (Print) 0027-8424 (Linking)
Abstract:		"Radiation of the plant pyridoxal 5'-phosphate (PLP)-dependent aromatic l-amino acid decarboxylase (AAAD) family has yielded an array of paralogous enzymes exhibiting divergent substrate preferences and catalytic mechanisms. Plant AAADs catalyze either the decarboxylation or decarboxylation-dependent oxidative deamination of aromatic l-amino acids to produce aromatic monoamines or aromatic acetaldehydes, respectively. These compounds serve as key precursors for the biosynthesis of several important classes of plant natural products, including indole alkaloids, benzylisoquinoline alkaloids, hydroxycinnamic acid amides, phenylacetaldehyde-derived floral volatiles, and tyrosol derivatives. Here, we present the crystal structures of four functionally distinct plant AAAD paralogs. Through structural and functional analyses, we identify variable structural features of the substrate-binding pocket that underlie the divergent evolution of substrate selectivity toward indole, phenyl, or hydroxyphenyl amino acids in plant AAADs. Moreover, we describe two mechanistic classes of independently arising mutations in AAAD paralogs leading to the convergent evolution of the derived aldehyde synthase activity. Applying knowledge learned from this study, we successfully engineered a shortened benzylisoquinoline alkaloid pathway to produce (S)-norcoclaurine in yeast. This work highlights the pliability of the AAAD fold that allows change of substrate selectivity and access to alternative catalytic mechanisms with only a few mutations"
Keywords:		"Amino Acids, Aromatic/chemistry/metabolism Aromatic-L-Amino-Acid Decarboxylases/*chemistry/genetics/metabolism *Catalytic Domain *Evolution, Molecular Plant Proteins/*chemistry/genetics/metabolism Substrate Specificity Aaad aromatic amino acid metabolism;"
Notes:		"MedlineTorrens-Spence, Michael P Chiang, Ying-Chih Smith, Tyler Vicent, Maria A Wang, Yi Weng, Jing-Ke eng P41 GM103403/GM/NIGMS NIH HHS/ S10 RR029205/RR/NCRR NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. 2020/05/07 Proc Natl Acad Sci U S A. 2020 May 19; 117(20):10806-10817. doi: 10.1073/pnas.1920097117. Epub 2020 May 5"