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タイトル: | Mechanism-based tuning of insect 3,4-dihydroxyphenylacetaldehyde synthase for synthetic bioproduction of benzylisoquinoline alkaloids |
著者: | Vavricka, Christopher J. Yoshida, Takanobu Kuriya, Yuki Takahashi, Shunsuke Ogawa, Teppei Ono, Fumie Agari, Kazuko Kiyota, Hiromasa Li, Jianyong Ishii, Jun Tsuge, Kenji Minami, Hiromichi Araki, Michihiro Hasunuma, Tomohisa Kondo, Akihiko |
著者名の別形: | 荒木, 通啓 |
キーワード: | General Biochemistry, Genetics and Molecular Biology General Physics and Astronomy General Chemistry |
発行日: | 1-May-2019 |
出版者: | Springer Science and Business Media LLC |
誌名: | Nature communications |
巻: | 10 |
論文番号: | 2015 |
抄録: | Previous studies have utilized monoamine oxidase (MAO) and L-3, 4-dihydroxyphenylalanine decarboxylase (DDC) for microbe-based production of tetrahydropapaveroline (THP), a benzylisoquinoline alkaloid (BIA) precursor to opioid analgesics. In the current study, a phylogenetically distinct Bombyx mori 3, 4-dihydroxyphenylacetaldehyde synthase (DHPAAS) is identified to bypass MAO and DDC for direct production of 3, 4-dihydroxyphenylacetaldehyde (DHPAA) from L-3, 4-dihydroxyphenylalanine (L-DOPA). Structure-based enzyme engineering of DHPAAS results in bifunctional switching between aldehyde synthase and decarboxylase activities. Output of dopamine and DHPAA products is fine-tuned by engineered DHPAAS variants with Phe79Tyr, Tyr80Phe and Asn192His catalytic substitutions. Balance of dopamine and DHPAA products enables improved THP biosynthesis via a symmetrical pathway in Escherichia coli. Rationally engineered insect DHPAAS produces (R, S)-THP in a single enzyme system directly from L-DOPA both in vitro and in vivo, at higher yields than that of the wild-type enzyme. However, DHPAAS-mediated downstream BIA production requires further improvement. |
記述: | An Author Correction to this article was published on 22 May 2019 |
著作権等: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
URI: | http://hdl.handle.net/2433/245405 |
DOI(出版社版): | 10.1038/s41467-019-09610-2 |
PubMed ID: | 31043610 |
関連リンク: | https://doi.org/10.1038/s41467-019-10312-y |
出現コレクション: | 学術雑誌掲載論文等 |
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