Evidence map›Paper›PMID 31043610›Full record

ArticleNature communications2019

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

Christopher J Vavricka, Takanobu Yoshida, Yuki Kuriya, Shunsuke Takahashi, Teppei Ogawa, Fumie Ono, Kazuko Agari, Hiromasa Kiyota, Jianyong Li, Jun Ishii and 5 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.1field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 46 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 6 institutions in 2 countries.

Christopher J VavrickaGraduate School of Science, Technology and Innovation, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, 657-8501, Japan.
Takanobu YoshidaGraduate School of Science, Technology and Innovation, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, 657-8501, Japan.
Yuki KuriyaGraduate School of Science, Technology and Innovation, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, 657-8501, Japan.
Shunsuke TakahashiGraduate School of Science, Technology and Innovation, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, 657-8501, Japan.ORCID http://orcid.org/0000-0003-0492-7906
Teppei OgawaMitsui Knowledge Industry Co., Ltd. (MKI), 2-3-33 Nakanoshima, Kita-ku, Osaka, 530-0005, Japan.
Fumie OnoGraduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan.
Kazuko AgariGraduate School of Science, Technology and Innovation, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, 657-8501, Japan.
Hiromasa KiyotaGraduate School of Environmental and Life Science, Okayama University, 1-1-1, Tsushima-Naka, Kita-ku, Okayama, 700-8530, Japan.
Jianyong LiDepartment of Biochemistry, Virginia Polytechnic and State University, 111 Engel Hall, Mail Code: 0308, Blacksburg, VA, 24061, USA.
Jun IshiiGraduate School of Science, Technology and Innovation, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, 657-8501, Japan.ORCID http://orcid.org/0000-0003-2568-515X
Kenji TsugeGraduate School of Science, Technology and Innovation, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, 657-8501, Japan.
Hiromichi MinamiResearch Institute for Bioresources and Biotechnology, Ishikawa Prefectural University, 1-308, Suematsu, Nonoichi-shi, Ishikawa-ken, 921-8836, Japan.
Michihiro ArakiGraduate School of Science, Technology and Innovation, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, 657-8501, Japan. araki@port.kobe-u.ac.jp.
Tomohisa HasunumaGraduate School of Science, Technology and Innovation, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, 657-8501, Japan. hasunuma@port.kobe-u.ac.jp.
Akihiko KondoGraduate School of Science, Technology and Innovation, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, 657-8501, Japan.ORCID http://orcid.org/0000-0003-1527-5288
Kobe University · JPKyoto University · JPIshikawa Prefectural University · JPMitsui (Japan) · JPOkayama University · JPVirginia Tech · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

3,4-Dihydroxyphenylacetic AcidAmino Acid MotifsAnimalsAromatic-L-Amino-Acid DecarboxylasesBombyxDopamineEscherichia coliInsect ProteinsMetabolic EngineeringRecombinant ProteinsStructure-Activity RelationshipTetrahydropapaveroline3,4-dihydroxyphenylacetaldehyde3,4-Dihydroxyphenylacetic AcidAromatic-L-Amino-Acid DecarboxylasesDopamineInsect ProteinsRecombinant ProteinsTetrahydropapaveroline

Identifiers

PMID31043610
PMCPMC6494836
OpenAlexW2942607895

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.