Evidence map›Paper›PMID 31699086›Full record

ArticleMicrobial cell factories2019

5-Aminolevulinic acid fermentation using engineered Saccharomyces cerevisiae.

Kiyotaka Y Hara, Masaru Saito, Hiroko Kato, Kana Morikawa, Hiroshi Kikukawa, Hironari Nomura, Takanori Fujimoto, Yoko Hirono-Hara, Shigeyuki Watanabe, Kengo Kanamaru and 1 more

Open access · goldAbstract read
In one paragraph

Article in Microbial cell factories, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

12 citing papers in PubMed, 45 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. The response mechanism analysis ofFrontiers in microbiology · 2024
    Article
  6. Enhancement of phycocyanobilin biosynthesis inSynthetic and systems biotechnology · 2023
    Article
  7. Genome-scale modeling drives 70-fold improvement of intracellular heme production inProceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  8. Article
  9. Review
  10. Review
  11. Review
  12. 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

11 authors at 3 institutions in 1 country.

Kiyotaka Y HaraDepartment of Environmental and Life Sciences, School of Food and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Suruga, Shizuoka, 422-8526, Japan. k-hara@u-shizuoka-ken.ac.jp.ORCID http://orcid.org/0000-0002-4477-6594
Masaru SaitoCosmo Oil Co., Ltd., 1-1-1 Shibaura, Minato-ku, Tokyo, 105-8528, Japan.
Hiroko KatoDepartment of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodaicho, Nada-ku, Kobe, 657-8501, Japan.
Kana MorikawaOrganization of Advanced Science and Technology, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, 657-8501, Japan.
Hiroshi KikukawaDepartment of Environmental and Life Sciences, School of Food and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Suruga, Shizuoka, 422-8526, Japan.
Hironari NomuraOrganization of Advanced Science and Technology, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, 657-8501, Japan.
Takanori FujimotoCosmo Oil Co., Ltd., 1-1-1 Shibaura, Minato-ku, Tokyo, 105-8528, Japan.
Yoko Hirono-HaraDepartment of Environmental and Life Sciences, School of Food and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Suruga, Shizuoka, 422-8526, Japan.
Shigeyuki WatanabeCosmo Oil Co., Ltd., 1-1-1 Shibaura, Minato-ku, Tokyo, 105-8528, Japan.
Kengo KanamaruDepartment of Applied Chemistry in Bioscience, Graduate School of Agricultural Science, Kobe University, Kobe, 657-8501, Japan.
Akihiko KondoDepartment of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodaicho, Nada-ku, Kobe, 657-8501, Japan. akondo@kobe-u.ac.jp.
Kobe University · JPCosmo Oil (Japan) · JPUniversity of Shizuoka · JP

Funding

Grant-in-Aid for Scientific Research (C) 16K00616JST-Mirai Program JPMJMI17EJ
6 · The paper itself

Abstract

background5'-Aminolevulinic acid (ALA) is widely used in the pharmaceutical industry, healthcare, and food production, and is a substrate for the biosynthesis of heme, which is required for respiration and photosynthesis. Enhancement of ALA biosynthesis has never been developed in Saccharomyces cerevisiae, which is a well-known model microorganism used for bioproduction of many value-added compounds.

resultsWe demonstrated that metabolic engineering significantly improved ALA production in S. cerevisiae. First, we found that overexpression of HEM1, which encodes ALA synthetase, increased ALA production. Furthermore, addition of an optimal amount of glycine, a substrate for ALA biosynthesis, or levulinic acid, an inhibitor of ALA dehydrogenase, effectively increased ALA production. Next, we developed an assay for multiple metabolites including ALA and found that aconitase, encoded by ACO1 and ACO2, is the rate-limiting enzyme of ALA biosynthesis when sufficient glycine is supplied. Overexpression of ACO2 further enhanced ALA production in S. cerevisiae overexpressing HEM1.

conclusionsIn this study, ALA production in S. cerevisiae was enhanced by metabolic engineering. This study also shows a strategy to identify the rate-limiting step of a target synthetic pathway by assay for multiple metabolites alongside the target product. This strategy can be applied to improve production of other valuable products in the well-studied and well-industrialized microorganism S. cerevisiae.

Indexed as

Saccharomyces cerevisiaeAconitate HydrataseAminolevulinic AcidFermentationGlycineLevulinic AcidsMetabolic EngineeringOrganisms, Genetically ModifiedSaccharomyces cerevisiae ProteinsAconitate HydrataseAminolevulinic AcidGlycineLevulinic AcidsSaccharomyces cerevisiae Proteins5′-Aminolevulinic acidCell factoryMetabolic engineeringSaccharomyces cerevisiaeYeast

Identifiers

PMID31699086
PMCPMC6839092
OpenAlexW2984063718

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.