Evidence map›Paper›PMID 39384562›Full record

ArticleNature communications2024

De novo production of protoberberine and benzophenanthridine alkaloids through metabolic engineering of yeast.

Xiang Jiao, Xiaozhi Fu, Qishuang Li, Junling Bu, Xiuyu Liu, Otto Savolainen, Luqi Huang, Juan Guo, Jens Nielsen, Yun Chen

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
–field-weighted citation impact
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

20 citing papers in PubMed.

  1. Metabolic engineering ofaBIOTECH · 2026
    Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Review
  12. Article
  13. Article
  14. Plants (Basel, Switzerland) · 2025
    Review
  15. Article
  16. Review
  17. Review
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Xiang JiaoDepartment of Life Sciences, Chalmers University of Technology, Kemivägen 10, SE-412 96, Gothenburg, Sweden.ORCID 0000-0001-8043-3719
Xiaozhi FuDepartment of Life Sciences, Chalmers University of Technology, Kemivägen 10, SE-412 96, Gothenburg, Sweden.ORCID 0000-0002-4465-7528
Qishuang LiState Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, 16 Neinanxiaojie, Dongcheng district, Beijing, China.ORCID 0000-0002-2148-7917
Junling BuState Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, 16 Neinanxiaojie, Dongcheng district, Beijing, China.
Xiuyu LiuState Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, 16 Neinanxiaojie, Dongcheng district, Beijing, China.
Otto SavolainenDepartment of Life Sciences, Chalmers University of Technology, Kemivägen 10, SE-412 96, Gothenburg, Sweden.
Luqi HuangState Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, 16 Neinanxiaojie, Dongcheng district, Beijing, China. huangluqi01@126.com.
Juan GuoState Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, 16 Neinanxiaojie, Dongcheng district, Beijing, China. guojuanzy@163.com.ORCID 0000-0002-1327-4428
Jens NielsenDepartment of Life Sciences, Chalmers University of Technology, Kemivägen 10, SE-412 96, Gothenburg, Sweden. nielsenj@chalmers.se.ORCID 0000-0002-9955-6003
Yun ChenDepartment of Life Sciences, Chalmers University of Technology, Kemivägen 10, SE-412 96, Gothenburg, Sweden. yunc@chalmers.se.ORCID 0000-0002-2146-6008

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Protoberberine alkaloids and benzophenanthridine alkaloids (BZDAs) are subgroups of benzylisoquinoline alkaloids (BIAs), which represent a diverse class of plant-specialized natural metabolites with many pharmacological properties. Microbial biosynthesis has been allowed for accessibility and scalable production of high-value BIAs. Here, we engineer Saccharomyces cerevisiae to de novo produce a series of protoberberines and BZDAs, including palmatine, berberine, chelerythrine, sanguinarine and chelirubine. An ER compartmentalization strategy is developed to improve vacuole protein berberine bridge enzyme (BBE) activity, resulting in >200% increase on the production of the key intermediate (S)-scoulerine. Another promiscuous vacuole protein dihydrobenzophenanthridine oxidase (DBOX) has been identified to catalyze two-electron oxidation on various tetrahydroprotoberberines at N7-C8 position and dihydrobenzophenanthridine alkaloids. Furthermore, cytosolically expressed DBOX can alleviate the limitation on BBE. This study highlights the potential of microbial cell factories for the biosynthesis of a diverse group of BIAs through engineering of heterologous plant enzymes.

Indexed as

BenzophenanthridinesBerberine AlkaloidsMetabolic EngineeringSaccharomyces cerevisiaeAlkaloidsBerberineAlkaloidsBenzophenanthridinesBerberineBerberine Alkaloidsprotoberberine

Identifiers

PMID39384562
PMCPMC11464499

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.