Biosynthesis of squalene from farnesyl diphosphate in Bacteria

Three steps catalyzed by three enzymes

Jian Jung Pan, Jose O. Solbiati, Gurusankar Ramamoorthy, Brandan S. Hillerich, Ronald D. Seidel, John E. Cronan, Steven C. Almo, C. Dale Poulter

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Squalene (SQ) is an intermediate in the biosynthesis of sterols in eukaryotes and a few bacteria and of hopanoids in bacteria where they promote membrane stability and the formation of lipid rafts in their hosts. The genes for hopanoid biosynthesis are typically located on clusters that consist of four highly conserved genes?hpnC, hpnD, hpnE, and hpnF?for conversion of farnesyl diphosphate (FPP) to hopene or related pentacyclic metabolites. While hpnF is known to encode a squalene cyclase, the functions for hpnC, hpnD, and hpnE are not rigorously established. The hpnC, hpnD, and hpnE genes from Zymomonas mobilis and Rhodopseudomonas palustris were cloned into Escherichia coli, a bacterium that does not contain genes homologous to hpnC, hpnD, and hpnE, and their functions were established in vitro and in vivo. HpnD catalyzes formation of presqualene diphosphate (PSPP) from two molecules of FPP; HpnC converts PSPP to hydroxysqualene (HSQ); and HpnE, a member of the amine oxidoreductase family, reduces HSQ to SQ. Collectively the reactions catalyzed by these three enzymes constitute a new pathway for biosynthesis of SQ in bacteria.

Original languageEnglish (US)
Pages (from-to)77-82
Number of pages6
JournalACS Central Science
Volume1
Issue number2
DOIs
StatePublished - May 27 2015

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Squalene
Biosynthesis
Bacteria
Enzymes
Genes
Sterols
Metabolites
Escherichia coli
Lipids
Amines
Oxidoreductases
Membranes
Molecules
farnesyl pyrophosphate
presqualene pyrophosphate

ASJC Scopus subject areas

  • Chemical Engineering(all)
  • Chemistry(all)

Cite this

Pan, J. J., Solbiati, J. O., Ramamoorthy, G., Hillerich, B. S., Seidel, R. D., Cronan, J. E., ... Poulter, C. D. (2015). Biosynthesis of squalene from farnesyl diphosphate in Bacteria: Three steps catalyzed by three enzymes. ACS Central Science, 1(2), 77-82. https://doi.org/10.1021/acscentsci.5b00115

Biosynthesis of squalene from farnesyl diphosphate in Bacteria : Three steps catalyzed by three enzymes. / Pan, Jian Jung; Solbiati, Jose O.; Ramamoorthy, Gurusankar; Hillerich, Brandan S.; Seidel, Ronald D.; Cronan, John E.; Almo, Steven C.; Poulter, C. Dale.

In: ACS Central Science, Vol. 1, No. 2, 27.05.2015, p. 77-82.

Research output: Contribution to journalArticle

Pan, JJ, Solbiati, JO, Ramamoorthy, G, Hillerich, BS, Seidel, RD, Cronan, JE, Almo, SC & Poulter, CD 2015, 'Biosynthesis of squalene from farnesyl diphosphate in Bacteria: Three steps catalyzed by three enzymes', ACS Central Science, vol. 1, no. 2, pp. 77-82. https://doi.org/10.1021/acscentsci.5b00115
Pan, Jian Jung ; Solbiati, Jose O. ; Ramamoorthy, Gurusankar ; Hillerich, Brandan S. ; Seidel, Ronald D. ; Cronan, John E. ; Almo, Steven C. ; Poulter, C. Dale. / Biosynthesis of squalene from farnesyl diphosphate in Bacteria : Three steps catalyzed by three enzymes. In: ACS Central Science. 2015 ; Vol. 1, No. 2. pp. 77-82.
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