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

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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.

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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

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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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Author notes

  1. Hui Wang

    Present address: Key Laboratory of Microorganism and Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, 518060, China

  2. Dinesh A. Nagegowda

    Present address: CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, India

Authors and Affiliations

  1. School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong, China

    Pan Liao, Hui Wang, Dinesh A. Nagegowda, Mingfu Wang & Mee-Len Chye

  2. Centre National de la Recherche Scientifique, UPR 2357, Institut de Biologie Moléculaire des Plantes, 67083, Strasbourg, France

    Andréa Hemmerlin & Thomas J. Bach

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  1. Pan Liao
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Correspondence to Mee-Len Chye.

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Communicated by N. Stewart.

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Liao, P., Wang, H., Hemmerlin, A. et al. Past achievements, current status and future perspectives of studies on 3-hydroxy-3-methylglutaryl-CoA synthase (HMGS) in the mevalonate (MVA) pathway. Plant Cell Rep 33, 1005–1022 (2014). https://doi.org/10.1007/s00299-014-1592-9

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