Evidence map›Paper›PMID 31226348›Full record

ArticleMetabolic engineering2019

Engineered mitochondrial production of monoterpenes in Saccharomyces cerevisiae.

Danielle A Yee, Anthony B DeNicola, John M Billingsley, Jenette G Creso, Vidya Subrahmanyam, Yi Tang

Open access · greenAbstract read
In one paragraph

Article in Metabolic engineering, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
6.0field-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

47 citing papers in PubMed, 152 citations in OpenAlex.

  1. Article
  2. Review
  3. Advances in mitochondrial compartmentalization for terpenoid synthesis inFrontiers in bioengineering and biotechnology · 2026
    Review
  4. Review
  5. Review
  6. Review
  7. Review
  8. Microbial biosynthesis of rare cannabinoids.Journal of industrial microbiology & biotechnology · 2024
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. EngineeringMetabolic engineering communications · 2023
    Article
  18. Article
  19. Review
  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

6 authors at 1 institution in 1 country.

Danielle A YeeDepartment of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA, 90095, United States.
Anthony B DeNicolaDepartment of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA, 90095, United States.
John M BillingsleyDepartment of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA, 90095, United States.
Jenette G CresoDepartment of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA, 90095, United States.
Vidya SubrahmanyamDepartment of Chemistry and Biochemistry, University of California, Los Angeles, CA, 90095, United States.
Yi TangDepartment of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA, 90095, United States; Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, 90095, United States. Electronic address: yitang@g.ucla.edu.
University of California, Los Angeles · US

Funding

CHEMISTRY BIOLOGY INTERFACE TRAINING PROGRAMT32GM008496 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MAYNARD, HEATHER D · 1993 to 2019
$6.3M
Engineering Yeast towards High Titer Production of Monoterpene Indole Alkaloid Natural ProductsR01AT010001 · NCCIH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Dino Di Carlo, Yi Tang · 2018 to 2026
$3.6M
Biotechnology Training in Biomedical Sciences and EngineeringT32GM067555 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GU, ZHEN · 2005 to 2019
$2.8M
NCCIH NIH HHS R01 AT010001NIGMS NIH HHS T32 GM008496NIGMS NIH HHS T32 GM067555
6 · The paper itself

Abstract

Monoterpene indole alkaloids (MIAs) from plants encompass a broad class of structurally complex and medicinally valuable natural products. MIAs are biologically derived from the universal precursor strictosidine. Although the strictosidine biosynthetic pathway has been identified and reconstituted, extensive work is required to optimize production of strictosidine and its precursors in yeast. In this study, we engineered a fully integrated and plasmid-free yeast strain with enhanced production of the monoterpene precursor geraniol. The geraniol biosynthetic pathway was targeted to the mitochondria to protect the GPP pool from consumption by the cytosolic ergosterol pathway. The mitochondrial geraniol producer showed a 6-fold increase in geraniol production compared to cytosolic producing strains. We further engineered the monoterpene-producing strain to synthesize the next intermediates in the strictosidine pathway: 8-hydroxygeraniol and nepetalactol. Integration of geraniol hydroxylase (G8H) from Catharanthus roseus led to essentially quantitative conversion of geraniol to 8-hydroxygeraniol at a titer of 227 mg/L in a fed-batch fermentation. Further introduction of geraniol oxidoreductase (GOR) and iridoid synthase (ISY) from C. roseus and tuning of the relative expression levels resulted in the first de novo nepetalactol production. The strategies developed in this work can facilitate future strain engineering for yeast production of later intermediates in the strictosidine biosynthetic pathway.

Indexed as

Metabolic EngineeringMicroorganisms, Genetically-ModifiedMitochondriaSaccharomyces cerevisiaeCatharanthusMitochondrial ProteinsMonoterpenesPlant ProteinsVinca AlkaloidsMitochondrial ProteinsMonoterpenesPlant ProteinsstrictosidineVinca Alkaloids

Identifiers

PMID31226348
PMCPMC6717016
OpenAlexW2951601171

What OpenQuestion holds

Textmetadata
LicenceTDM
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.