Structural basis for divergent and convergent evolution of catalytic machineries in plant aromatic amino acid decarboxylase proteins
© 2020 National Academy of Sciences. All rights reserved. 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 cataly...
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| Format: | Article |
| Language: | English |
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Proceedings of the National Academy of Sciences
2021
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| Online Access: | https://hdl.handle.net/1721.1/134398 |
| _version_ | 1811079251792756736 |
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| author | Torrens-Spence, Michael P Chiang, Ying-Chih Smith, Tyler Vicent, Maria A Wang, Yi Weng, Jing-Ke |
| author2 | Whitehead Institute for Biomedical Research |
| author_facet | Whitehead Institute for Biomedical Research Torrens-Spence, Michael P Chiang, Ying-Chih Smith, Tyler Vicent, Maria A Wang, Yi Weng, Jing-Ke |
| author_sort | Torrens-Spence, Michael P |
| collection | MIT |
| description | © 2020 National Academy of Sciences. All rights reserved. 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. |
| first_indexed | 2024-09-23T11:12:15Z |
| format | Article |
| id | mit-1721.1/134398 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:12:15Z |
| publishDate | 2021 |
| publisher | Proceedings of the National Academy of Sciences |
| record_format | dspace |
| spelling | mit-1721.1/1343982023-09-27T17:38:29Z Structural basis for divergent and convergent evolution of catalytic machineries in plant aromatic amino acid decarboxylase proteins Torrens-Spence, Michael P Chiang, Ying-Chih Smith, Tyler Vicent, Maria A Wang, Yi Weng, Jing-Ke Whitehead Institute for Biomedical Research Massachusetts Institute of Technology. Department of Biology © 2020 National Academy of Sciences. All rights reserved. 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. 2021-10-27T20:04:50Z 2021-10-27T20:04:50Z 2020 2021-08-04T14:44:16Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/134398 en 10.1073/PNAS.1920097117 Proceedings of the National Academy of Sciences of the United States of America Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Proceedings of the National Academy of Sciences PNAS |
| spellingShingle | Torrens-Spence, Michael P Chiang, Ying-Chih Smith, Tyler Vicent, Maria A Wang, Yi Weng, Jing-Ke Structural basis for divergent and convergent evolution of catalytic machineries in plant aromatic amino acid decarboxylase proteins |
| title | Structural basis for divergent and convergent evolution of catalytic machineries in plant aromatic amino acid decarboxylase proteins |
| title_full | Structural basis for divergent and convergent evolution of catalytic machineries in plant aromatic amino acid decarboxylase proteins |
| title_fullStr | Structural basis for divergent and convergent evolution of catalytic machineries in plant aromatic amino acid decarboxylase proteins |
| title_full_unstemmed | Structural basis for divergent and convergent evolution of catalytic machineries in plant aromatic amino acid decarboxylase proteins |
| title_short | Structural basis for divergent and convergent evolution of catalytic machineries in plant aromatic amino acid decarboxylase proteins |
| title_sort | structural basis for divergent and convergent evolution of catalytic machineries in plant aromatic amino acid decarboxylase proteins |
| url | https://hdl.handle.net/1721.1/134398 |
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