Polyisoprenoids – Secondary metabolites or physiologically important superlipids?

Surmacz, Liliana; Świeżewska, Ewa

doi:10.1016/j.bbrc.2011.03.059

Cited by 95 publications

(114 citation statements)

References 55 publications

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“…Polyisoprenyl monophosphates of different lengths and saturation (dolichol or undecaprenol derivatives) are utilized as pyrophosphate lipid carriers (Jones et al, 2009;Surmacz & Swiezewska, 2011;Swiezewska & Danikiewicz, 2005) in N-and O-linked protein glycosylation pathways in all three domains of life, i.e. eukaryotes, bacteria and archaea (Calo et al, 2010;Helenius & Aebi, 2004;Jones et al, 2009;Larkin & Imperiali, 2011;Nothaft & Szymanski, 2010;Schwarz & Aebi, 2011;Weerapana & Imperiali, 2006).…”

Section: Introductionmentioning

confidence: 99%

“…The first class includes the undecaprenyl (C 55 ) lipid carriers, which are unsaturated and consist of both trans and cis units in bacteria, while plant undecaprenols vary in length with some in the all-trans configuration (Hartley & Imperiali, 2012;Surmacz & Swiezewska, 2011;Swiezewska & Danikiewicz, 2005). The second class, dolichols, are lipid carriers of varying lengths found in animals, plants and archaea.…”

Section: Introductionmentioning

confidence: 99%

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Conservation of the PTEN catalytic motif in the bacterial undecaprenyl pyrophosphate phosphatase, BacA/UppP

Bickford

Nick

2013

Microbiology

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Isoprenoid lipid carriers are essential in protein glycosylation and bacterial cell envelope biosynthesis. The enzymes involved in their metabolism (synthases, kinases and phosphatases) are therefore critical to cell viability. In this review, we focus on two broad groups of isoprenoid pyrophosphate phosphatases. One group, containing phosphatidic acid phosphatase motifs, includes the eukaryotic dolichyl pyrophosphate phosphatases and proposed recycling bacterial undecaprenol pyrophosphate phosphatases, PgpB, YbjB and YeiU/LpxT. The second group comprises the bacterial undecaprenol pyrophosphate phosphatase, BacA/UppP, responsible for initial formation of undecaprenyl phosphate, which we predict contains a tyrosine phosphate phosphatase motif resembling that of the tumour suppressor, phosphatase and tensin homologue (PTEN). Based on protein sequence alignments across species and 2D structure predictions, we propose catalytic and lipid recognition motifs unique to BacA/UppP enzymes. The verification of our proposed active-site residues would provide new strategies for the development of substratespecific inhibitors which mimic both the lipid and pyrophosphate moieties, leading to the development of novel antimicrobial agents.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Conservation of the PTEN catalytic motif in the bacterial undecaprenyl pyrophosphate phosphatase, BacA/UppP

Bickford

Nick

2013

Microbiology

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“…Arabidopsis (Arabidopsis thaliana) hairy roots contain a complex Dol mixture comprising three groups (families) differing in chain length (Jozwiak et al, 2013). Their biosynthesis is catalyzed by cisprenyltransferases (CPTs), and six out of nine putative CPT-encoding genes of Arabidopsis are expressed in roots (Surmacz and Swiezewska, 2011). Eukaryotic CPT performs sequential condensations of the IPP with an all-trans-initiator to form a mixture of homologous polyprenyl diphosphates, which subsequently are converted to Dols according to tissue-specific requirements (Cantagrel et al, 2010;Jozwiak et al, 2015).…”

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confidence: 99%

Modeling of Dolichol Mass Spectra Isotopic Envelopes as a Tool to Monitor Isoprenoid Biosynthesis

et al. 2017

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The cooperation of the mevalonate (MVA) and methylerythritol phosphate (MEP) pathways, operating in parallel in plants to generate isoprenoid precursors, has been studied extensively. Elucidation of the isoprenoid metabolic pathways is indispensable for the rational design of plant and microbial systems for the production of industrially valuable terpenoids. Here, we describe a new method, based on numerical modeling of mass spectra of metabolically labeled dolichols (Dols), designed to quantitatively follow the cooperation of MVA and MEP reprogrammed upon osmotic stress (sorbitol treatment) in Arabidopsis (Arabidopsis thaliana). The contribution of the MEP pathway increased significantly (reaching 100%) exclusively for the dominating Dols, while for long-chain Dols, the relative input of the MEP and MVA pathways remained unchanged, suggesting divergent sites of synthesis for dominating and long-chain Dols. The analysis of numerically modeled Dol mass spectra is a novel method to follow modulation of the concomitant activity of isoprenoid-generating pathways in plant cells; additionally, it suggests an exchange of isoprenoid intermediates between plastids and peroxisomes.Isopentenyl diphosphate (IPP), the building block of isoprenoids, the most numerous class of secondary metabolites, is derived in plants from two pathways operating in parallel: the cytoplasmic mevalonate (MVA) and the plastidic methylerythritol phosphate (MEP) pathways (Rohmer, 1999;Pulido et al., 2012).Analysis of over 130 isoprenoids has shown that, in angiosperms under standard growth conditions, carotenoids and chlorophyll phytyl chains on the one hand and phytosterols on the other are made nearly exclusively via a single pathway (MEP and MVA, respectively), while numerous other isoprenoids, including dolichols (Dols; Skorupinska-Tudek et al., 2008), are of mixed origin (Hemmerlin et al., 2012).The cooperation of the two pathways (often called cross talk) is considered essential for plant adaptive responses to biotic and abiotic stresses. Consequently, their relative contributions to the formation of IPP are modulated, and the expression of particular genes of the MVA and MEP pathways is frequently correlated with stress (pathogen attack, elicitation, wounding, etc.;Hemmerlin et al., 2012) or plant development (Opitz et al., 2014). Interestingly, the effect of stress on the regulation of the MEP-MVA balance has so far been analyzed only qualitatively.Several methodologies have been employed to unravel the relative contributions of the MVA and MEP pathways to isoprenoids, such as metabolic labeling with isotopically labeled precursors (stable isotopes or radioisotopes were used), followed by structural analysis of the product of interest or blockage of the pathway (chemical, with pathway-specific inhibitors, or genetic), followed by quantification of the isoprenoid intermediates and/or end products. The advantages

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“…An important class of membrane-associated pathways involves the assembly of complex glycoconjugates, which is dependent on extended linear polyprenols (1)(2)(3)(4). The products of these pathways are essential for cellular viability in all domains of life and, intriguingly, the polyprenols that are used in glycan assembly vary between organisms, with considerable differences in the overall length and degrees of unsaturation (2,5). For example, bacteria generate peptidoglycan components on the membraneanchored undecaprenyl-diphosphate before cell wall assembly (6), whereas eukaryotes produce glycans for N-linked protein glycosylation via dolichyl-diphosphate-linked intermediates, which feature polyprenols ranging from 14-25 isoprene units (1,2,7).…”

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confidence: 99%

Lipid bilayer nanodisc platform for investigating polyprenol-dependent enzyme interactions and activities

Hartley

Schneggenburger

Imperiali

2013

Proc. Natl. Acad. Sci. U.S.A.

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Membrane-bound polyprenol-dependent pathways are important for the assembly of essential glycoconjugates in all domains of life. However, despite their prevalence, the functional significance of the extended linear polyprenyl groups in the interactions of the glycan substrates, the biosynthetic enzymes that act upon them, and the membrane bilayer in which they are embedded remains a mystery. These interactions are investigated simultaneously and uniquely through application of the nanodisc membrane technology. The Campylobacter jejuni N-linked glycosylation pathway has been chosen as a model pathway in which all of the enzymes and substrates are biochemically accessible. We present the functional reconstitution of two enzymes responsible for the early membrane-committed steps in glycan assembly. Protein stoichiometry analysis, fluorescence-based approaches, and biochemical activity assays are used to demonstrate the colocalization of the two enzymes in nanodiscs. Isotopic labeling of the substrates reveals that undecaprenyl-phosphate is coincorporated into discs with the two enzymes, and furthermore, that both enzymes are functionally reconstituted and can sequentially convert the coembedded undecaprenyl-phosphate into undecaprenyl-diphosphate-linked disaccharide. These studies provide a proof-of-concept demonstrating that the nanodisc model membrane system represents a promising experimental platform for analyzing the multifaceted interactions among the enzymes involved in polyprenol-dependent glycan assembly pathways, the membrane-associated substrates, and the lipid bilayer. The stage is now set for exploration of the roles of the conserved polyprenols in promoting protein-protein interactions among pathway enzymes and processing of substrates through sequential steps in membrane-associated glycan assembly.

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Polyisoprenoids – Secondary metabolites or physiologically important superlipids?

Cited by 95 publications

References 55 publications

Conservation of the PTEN catalytic motif in the bacterial undecaprenyl pyrophosphate phosphatase, BacA/UppP

Conservation of the PTEN catalytic motif in the bacterial undecaprenyl pyrophosphate phosphatase, BacA/UppP

Modeling of Dolichol Mass Spectra Isotopic Envelopes as a Tool to Monitor Isoprenoid Biosynthesis

Lipid bilayer nanodisc platform for investigating polyprenol-dependent enzyme interactions and activities

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