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


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.


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.


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



Acetoacetyl-CoA thiolase

A. thaliana

Arabidopsis thaliana


Arabidopsis thaliana HMGS

B. juncea

Brassica juncea


Brassica juncea HMGS




Brassinosteroid-6-oxidase 2

C. acuminate

Camptotheca acuminate


Camptotheca acuminate HMGS


Coenzyme A


Copalyl diphosphate synthase

C. roseus

Catharanthus roseus


C. roseus HMGS


C-22 sterol desaturase


A cytochrome P450 enzyme




Dithiobisnitrobenzoic acid


Δ24 Sterol reductase


1-Deoxy-d-xylulose 5-phosphate reductoisomerase


1-Deoxy-d-xylulose 5-phosphate synthase


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


Glyceraldehyde 3-phosphate


Gas chromatography–mass spectrometry

G. gallus

Gallus gallus


Gallus gallus HMGS (cytosolic)

H. brasiliensis

Hevea brasiliensis


Hevea brasiliensis HMGS


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


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




HMG-CoA synthase


HMG-CoA reductase


High-performance liquid chromatography

H. sapiens

Homo sapiens


Homo sapiens HMGS (cytosolic)


Homo sapiens HMGS2 (mitochondrial)


Isopentenyl diphosphate isomerase


Insulin-induced gene protein


Isopentenyl diphosphate


Ent-kaurene synthase-like

M. auratus

Mesocricetus auratus


Mesocricetus auratus HMGS (cytosolic)


Mesocricetus auratus HMGS (mitochondrial variant 1)


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


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


2C-methyl-d-erythritol 4-phosphate


Methyl jasmonate


Mevalonate kinase






Open reading frame

O. sativa

Oryza sativa


Oryza sativa HMGS


Inorganic phosphate


Phosphomevalonate kinase


Diphosphomevalonate decarboxylase


Mevalonate 5-diphosphate



P. sylvestris

Pinus sylvestris


Pinus sylvestris HMGS


Coenzyme Q10


Rapid amplification of cDNA ends

R. norvegicus

Rattus norvegicus


Rattus norvegicus HMGS (cytosolic)


Rattus norvegicus HMGS (mitochondrial)


Reverse transcriptase-polymerase chain reaction


Salicylic acid


SREBP cleavage-activating protein

S. lycopersicum

Solanum lycopersicum


Solanum lycopersicum HMGS

S. miltiorrhiza

Salvia miltiorrhiza


Salvia miltiorrhiza HMGS


Sterol methyltransferase 2


Sterol regulatory element-binding proteins

S. scrofa

Sus scrofa


Sus scrofa (mitochondrial)

T. media

Taxus × media


Taxus × media HMGS



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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