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90005962

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Mechanism-based tuning of insect 3,4-dihydroxyphenylacetaldehyde synthase for synthetic bioproduction of benzylisoquinoline alkaloids

A2048 / / / A2015 / / / / / / A1290 / A1273 / / A0291 / A0960 / A1715

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

VAVRICKA, JR, CHRISTOPHER, JOHN / / / 高橋, 俊介 / / / / / / 石井, 純 / 柘植, 謙爾 / / 荒木, 通啓 / 蓮沼, 誠久 / 近藤, 昭彦

10

2015

Nature Publishing Group

2019-05-01

A correction has been published: Nature Communications 10 :2336. May 22, 2019, https://doi.org/10.1038/s41467-019-10312-y

© The Author(s) 2019. 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/.

2019-05-17

20411723

eng

/ / / / / / / / / 1000040512546 / 1000070399690 / / 1000040396867 / 1000020529606 / 1000040205547

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.

http://kuid.ofc.kobe-u.ac.jp/InfoSearch/html/researcher/researcher_Ou862l9fQeXO-IBQ3mbe3w_ja.html / / / http://kuid.ofc.kobe-u.ac.jp/InfoSearch/html/researcher/researcher_bROXx_p5SUTO-IBQ3mbe3w_ja.html / / / / / / http://kuid.ofc.kobe-u.ac.jp/InfoSearch/html/researcher/researcher_lnOwcnbFKwXO-IBQ3mbe3w_ja.html / http://kuid.ofc.kobe-u.ac.jp/InfoSearch/html/researcher/researcher_P4nnmdJ8T2HO-IBQ3mbe3w_ja.html / / / http://kuid.ofc.kobe-u.ac.jp/InfoSearch/html/researcher/researcher_tCaVvIMA_WbO-IBQ3mbe3w_ja.html / http://kuid.ofc.kobe-u.ac.jp/InfoSearch/html/researcher/researcher_xfAUsj7HKdXO-IBQ3mbe3w_ja.html

2019-05-17