Overexpressing 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase (HMGR) in the Lactococcal Mevalonate Pathway for Heterologous Plant Sesquiterpene Production

Adelene Ai Lian Song, Janna Ong Abdullah, Mohd Puad Abdullah, Norazizah Shafee, Roohaida Othman, Ee Fun Tan, Normah Mohd. Noor, Abdul Rahim Raha

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Isoprenoids are a large and diverse group of metabolites with interesting properties such as flavour, fragrance and therapeutic properties. They are produced via two pathways, the mevalonate pathway or the 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway. While plants are the richest source of isoprenoids, they are not the most efficient producers. Escherichia coli and yeasts have been extensively studied as heterologous hosts for plant isoprenoids production. In the current study, we describe the usage of the food grade Lactococcus lactis as a potential heterologous host for the production of sesquiterpenes from a local herbaceous Malaysian plant, Persicaria minor (synonym Polygonum minus). A sesquiterpene synthase gene from P. minor was successfully cloned and expressed in L. lactis. The expressed protein was identified to be a β-sesquiphellandrene synthase as it was demonstrated to be functional in producing β-sesquiphellandrene at 85.4% of the total sesquiterpenes produced based on in vitro enzymatic assays. The recombinant L. lactis strain developed in this study was also capable of producing β-sesquiphellandrene in vivo without exogenous substrates supplementation. In addition, overexpression of the strain's endogenous 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMGR), an established rate-limiting enzyme in the eukaryotic mevalonate pathway, increased the production level of β-sesquiphellandrene by 1.25-1.60 fold. The highest amount achieved was 33 nM at 2 h post-induction.

Original languageEnglish
Article numbere52444
JournalPLoS One
Volume7
Issue number12
DOIs
Publication statusPublished - 29 Dec 2012

Fingerprint

Mevalonic Acid
Lactococcus lactis
Sesquiterpenes
isoprenoids
Terpenes
sesquiterpenoids
Oxidoreductases
Polygonum
erythritol
Fragrances
food grades
medicinal properties
Flavors
Enzyme Assays
Metabolites
Yeast
Escherichia coli
Assays
host plants
flavor

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Overexpressing 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase (HMGR) in the Lactococcal Mevalonate Pathway for Heterologous Plant Sesquiterpene Production. / Song, Adelene Ai Lian; Abdullah, Janna Ong; Abdullah, Mohd Puad; Shafee, Norazizah; Othman, Roohaida; Tan, Ee Fun; Mohd. Noor, Normah; Raha, Abdul Rahim.

In: PLoS One, Vol. 7, No. 12, e52444, 29.12.2012.

Research output: Contribution to journalArticle

Song, Adelene Ai Lian ; Abdullah, Janna Ong ; Abdullah, Mohd Puad ; Shafee, Norazizah ; Othman, Roohaida ; Tan, Ee Fun ; Mohd. Noor, Normah ; Raha, Abdul Rahim. / Overexpressing 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase (HMGR) in the Lactococcal Mevalonate Pathway for Heterologous Plant Sesquiterpene Production. In: PLoS One. 2012 ; Vol. 7, No. 12.
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