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Plant Cell Reports

, Volume 33, Issue 7, pp 1005–1022 | Cite as

Past achievements, current status and future perspectives of studies on 3-hydroxy-3-methylglutaryl-CoA synthase (HMGS) in the mevalonate (MVA) pathway

  • Pan Liao
  • Hui Wang
  • Andréa Hemmerlin
  • Dinesh A. Nagegowda
  • Thomas J. Bach
  • Mingfu Wang
  • Mee-Len ChyeEmail author
Review

Abstract

Key message

HMGS functions in phytosterol biosynthesis, development and stress responses. F-244 could specifically-inhibit HMGS in tobacco BY-2 cells and Brassica seedlings. An update on HMGS from higher plants is presented.

Abstract

3-Hydroxy-3-methylglutaryl-coenzyme A synthase (HMGS) is the second enzyme in the mevalonate pathway of isoprenoid biosynthesis and catalyzes the condensation of acetoacetyl-CoA and acetyl-CoA to produce S-3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). Besides HMG-CoA reductase (HMGR), HMGS is another key enzyme in the regulation of cholesterol and ketone bodies in mammals. In plants, it plays an important role in phytosterol biosynthesis. Here, we summarize the past investigations on eukaryotic HMGS with particular focus on plant HMGS, its enzymatic properties, gene expression, protein structure, and its current status of research in China. An update of the findings on HMGS from animals (human, rat, avian) to plants (Brassica juncea, Hevea brasiliensis, Arabidopsis thaliana) will be discussed. Current studies on HMGS have been vastly promoted by developments in biochemistry and molecular biology. Nonetheless, several limitations have been encountered, thus some novel advances in HMGS-related research that have recently emerged will be touched on.

Keywords

Acetyl-CoA Acetoacetyl-CoA HMG-CoA HMGS Sterol Brassinosteroid 

Abbreviations

AACT

Acetoacetyl-CoA thiolase

A. thaliana

Arabidopsis thaliana

AtHMGS

Arabidopsis thaliana HMGS

B. juncea

Brassica juncea

BjHMGS

Brassica juncea HMGS

BRs

Brassinosteroids

BR60X2

Brassinosteroid-6-oxidase 2

C. acuminate

Camptotheca acuminate

CaHMGS

Camptotheca acuminate HMGS

CoASH

Coenzyme A

CPS

Copalyl diphosphate synthase

C. roseus

Catharanthus roseus

CrHMGS

C. roseus HMGS

CYP710A1

C-22 sterol desaturase

CYP76AH1

A cytochrome P450 enzyme

DAP

Days-after-pollination

DTNB

Dithiobisnitrobenzoic acid

DWF1

Δ24 Sterol reductase

DXR

1-Deoxy-d-xylulose 5-phosphate reductoisomerase

DXS

1-Deoxy-d-xylulose 5-phosphate synthase

F-244

3,5,7-Trimethyl-12-hydroxy-13-hydroxymethyl-2,4-tetradecadiendioic acid 12,14-lactone

GA-3-P

Glyceraldehyde 3-phosphate

GC–MS

Gas chromatography–mass spectrometry

G. gallus

Gallus gallus

GgHMGS C

Gallus gallus HMGS (cytosolic)

H. brasiliensis

Hevea brasiliensis

HbHMGS

Hevea brasiliensis HMGS

HDR

1-Hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase

HDS

1-Hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate synthase

HMG-CoA

S-3-Hydroxy-3-methylglutaryl-CoA

HMGS

HMG-CoA synthase

HMGR

HMG-CoA reductase

HPLC

High-performance liquid chromatography

H. sapiens

Homo sapiens

HsHMGS C

Homo sapiens HMGS (cytosolic)

HsHMGS2 M

Homo sapiens HMGS2 (mitochondrial)

IDI

Isopentenyl diphosphate isomerase

INSIG

Insulin-induced gene protein

IPP

Isopentenyl diphosphate

KSL

Ent-kaurene synthase-like

M. auratus

Mesocricetus auratus

MaHMGS C

Mesocricetus auratus HMGS (cytosolic)

MaHMGS M1

Mesocricetus auratus HMGS (mitochondrial variant 1)

MCT

2C-methyl-d-erythritol 4-phosphate cytidyl transferase

MDS

2C-methyl-d-erythritol 2,4-cyclodiphosphate synthase

MEP

2C-methyl-d-erythritol 4-phosphate

MJ

Methyl jasmonate

MK

Mevalonate kinase

MVA

Mevalonate

OE

Overexpressors

ORF

Open reading frame

O. sativa

Oryza sativa

OsHMGS

Oryza sativa HMGS

Pi

Inorganic phosphate

PMK

Phosphomevalonate kinase

PPMD

Diphosphomevalonate decarboxylase

PP-MVA

Mevalonate 5-diphosphate

PR

Pathogenesis-related

P. sylvestris

Pinus sylvestris

PsHMGS

Pinus sylvestris HMGS

Q10

Coenzyme Q10

RACE

Rapid amplification of cDNA ends

R. norvegicus

Rattus norvegicus

RnHMGS C

Rattus norvegicus HMGS (cytosolic)

RnHMGS M

Rattus norvegicus HMGS (mitochondrial)

RT-PCR

Reverse transcriptase-polymerase chain reaction

SA

Salicylic acid

SCAP

SREBP cleavage-activating protein

S. lycopersicum

Solanum lycopersicum

SlHMGS

Solanum lycopersicum HMGS

S. miltiorrhiza

Salvia miltiorrhiza

SmHMGS

Salvia miltiorrhiza HMGS

SMT2

Sterol methyltransferase 2

SREBPs

Sterol regulatory element-binding proteins

S. scrofa

Sus scrofa

SsHMGS M

Sus scrofa (mitochondrial)

T. media

Taxus × media

TmHMGS

Taxus × media HMGS

Notes

Acknowledgments

This work was supported by the Wilson and Amelia Wong Endowment Fund and the University of Hong Kong [CRCG 10400945, CRCG 104001061, University Postgraduate Fellowship (PL) and a studentship (HW)].

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Pan Liao
    • 1
  • Hui Wang
    • 1
    • 2
  • Andréa Hemmerlin
    • 3
  • Dinesh A. Nagegowda
    • 1
    • 4
  • Thomas J. Bach
    • 3
  • Mingfu Wang
    • 1
  • Mee-Len Chye
    • 1
    Email author
  1. 1.School of Biological SciencesThe University of Hong KongHong KongChina
  2. 2.Key Laboratory of Microorganism and Genetic Engineering, College of Life SciencesShenzhen UniversityShenzhenChina
  3. 3.Centre National de la Recherche ScientifiqueUPR 2357, Institut de Biologie Moléculaire des PlantesStrasbourgFrance
  4. 4.CSIR-Central Institute of Medicinal and Aromatic PlantsLucknowIndia

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