Evidence map›Paper›PMID 33273470›Full record

ArticleNature communications2020

Pathway engineering in yeast for synthesizing the complex polyketide bikaverin.

Meng Zhao, Yu Zhao, Mingdong Yao, Hala Iqbal, Qi Hu, Hong Liu, Bin Qiao, Chun Li, Christine A S Skovbjerg, Jens Christian Nielsen and 4 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
5.7field-weighted citation impact, top 3% 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

22 citing papers in PubMed, 62 citations in OpenAlex.

  1. Design of an oral vaccine againstThe veterinary quarterly · 2026
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  8. Redesigned Pathway forJACS Au · 2025
    Article
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  14. Rethinking Biosynthesis of Aclacinomycin A.Molecules (Basel, Switzerland) · 2023
    Review
  15. Review
  16. Article
  17. Expression of bik cluster and production of bikaverin by Fusarium oxysporum f. sp. lycopersici grown using two alternate nitrogen sources.International microbiology : the official journal of the Spanish Society for Microbiology · 2022
    Article
  18. Review
  19. Article
  20. Review
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

14 authors at 5 institutions in 5 countries.

Meng ZhaoFrontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, 300072, Tianjin, PR China.ORCID 0000-0001-6253-8154
Yu ZhaoInstitute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, NYU Langone Health, New York, NY, 10016, USA.ORCID 0000-0003-4659-9832
Mingdong YaoFrontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, 300072, Tianjin, PR China.
Hala IqbalInstitute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, NYU Langone Health, New York, NY, 10016, USA.ORCID 0000-0003-3437-2139
Qi HuFrontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, 300072, Tianjin, PR China.
Hong LiuFrontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, 300072, Tianjin, PR China.
Bin QiaoFrontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, 300072, Tianjin, PR China.
Chun LiFrontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, 300072, Tianjin, PR China.ORCID 0000-0003-4262-6848
Christine A S SkovbjergSection for Synthetic Biology, Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads, Building 223, Kongens Lyngby, Denmark.ORCID 0000-0003-4790-718X
Jens Christian NielsenDepartment of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.
Jens NielsenDepartment of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.ORCID 0000-0002-9955-6003
Rasmus J N FrandsenSection for Synthetic Biology, Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads, Building 223, Kongens Lyngby, Denmark.ORCID 0000-0002-3799-6062
Yingjin YuanFrontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, 300072, Tianjin, PR China.ORCID 0000-0003-0553-0089
Jef D BoekeInstitute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, NYU Langone Health, New York, NY, 10016, USA. jef.boeke@nyulangone.org.ORCID 0000-0001-5322-4946
Tianjin University · CNInstitute for Systems Biology · USNovo Nordisk Foundation · DKTechnical University of Denmark · DKNYU Langone Health · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Fungal polyketides display remarkable structural diversity and bioactivity, and therefore the biosynthesis and engineering of this large class of molecules is therapeutically significant. Here, we successfully recode, construct and characterize the biosynthetic pathway of bikaverin, a tetracyclic polyketide with antibiotic, antifungal and anticancer properties, in S. cerevisiae. We use a green fluorescent protein (GFP) mapping strategy to identify the low expression of Bik1 (polyketide synthase) as a major bottleneck step in the pathway, and a promoter exchange strategy is used to increase expression of Bik1 and bikaverin titer. Then, we use an enzyme-fusion strategy to directly couple the monooxygenase (Bik2) and methyltransferase (Bik3) to efficiently channel intermediates between modifying enzymes, leading to an improved titer of bikaverin at 202.75 mg/L with flask fermentation (273-fold higher than the initial titer). This study demonstrates that the biosynthesis of complex fungal polyketides can be established and efficiently engineered in S. cerevisiae, highlighting the potential for natural product synthesis and large-scale fermentation in yeast.

Indexed as

Biosynthetic PathwaysMetabolic EngineeringGreen Fluorescent ProteinsPolyketidesSaccharomyces cerevisiaeXanthonesbikaverinGreen Fluorescent ProteinsPolyketidesXanthones

Identifiers

PMID33273470
PMCPMC7713123
OpenAlexW3110585069

What OpenQuestion 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 OpenQuestion graph.