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Hopanoid lipids: from membranes to plant–bacteria interactions

Key Points

  • Hopanes were discovered by petroleum geologists as ubiquitous molecular fossils in ancient sedimentary rocks. Later, bacterial hopanoids were identified as their progenitors.

  • Today, phylogenetically diverse bacteria make hopanoids using machinery encoded by a conserved set of genes. The rhizosphere appears to be a niche that is common to many hopanoid-producing bacteria, and some hopanoid producers are known plant symbionts.

  • Bacteria make structurally distinct types of hopanoids, including ones that can covalently bind lipid A. Different hopanoid classes exhibit different properties and likely have specific biological functions.

  • Hopanoids share similar biophysical properties with sterols, such as tuning membrane rigidity and permeability. Though some evidence suggests that hopanoids help order membranes, how such ordering impacts cells and whether hopanoids interact with particular membrane proteins remain to be determined.

  • In vitro, hopanoids contribute to bacterial stress resistance, which may help explain their ability to facilitate beneficial plant–bacteria interactions. However, given that hopanoids can also serve as carriers for plant hormones and that plants themselves make hopanoid-like compounds, it is likely that other mechanisms are additionally at play.

Abstract

Lipid research represents a frontier for microbiology, as showcased by hopanoid lipids. Hopanoids, which resemble sterols and are found in the membranes of diverse bacteria, have left an extensive molecular fossil record. They were first discovered by petroleum geologists. Today, hopanoid-producing bacteria remain abundant in various ecosystems, such as the rhizosphere. Recently, great progress has been made in our understanding of hopanoid biosynthesis, facilitated in part by technical advances in lipid identification and quantification. A variety of genetically tractable, hopanoid-producing bacteria have been cultured, and tools to manipulate hopanoid biosynthesis and detect hopanoids are improving. However, we still have much to learn regarding how hopanoid production is regulated, how hopanoids act biophysically and biochemically, and how their production affects bacterial interactions with other organisms, such as plants. The study of hopanoids thus offers rich opportunities for discovery.

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Figure 1: Pathways of sterol and hopanoid biosynthesis.
Figure 2: Regulation of lipid raft formation by hopanoids.
Figure 3: Hopanoid-rich vesicles in Frankia spp.
Figure 4: Chemical structure of hopanoid-lipid A from Bradyrhizobium spp.

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Acknowledgements

The authors thank A. Session, P. Normand and the reviewers for constructive comments on the manuscript. We appreciate permission from D. Benson, A. Berry and J. Sáenz to reproduce images from their work. Grants from the Howard Hughes Medical Institute (HHMI; D.K.N.), National Aeronautics and Space Administration (NASA; NNX12AD93G, D.K.N.), the Jane Coffin Childs Memorial Fund (B.J.B.), the US National Institutes of Health (NIH; K99GM126141, B.J.B.), H2020- MSCA-ITN-2014-ETN TOLLerant (A.S.), Progetto Galileo G14-23 (A.S.), Mizutani Foundation for Glycoscience 2014 (A.M.) and the French National Research Agency (ANR-BugsInaCell-13-BSV7-0013) have sustained our research on this problem.

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B.J.B, E.G., A.S. and D.K.N. researched data for the article. B.J.B., E.G., A.M., A.S. and D.K.N. substantially contributed to the discussion of content. B.J.B., N.B., E.G., A.S. and D.K.N. wrote the article. All authors reviewed and edited the manuscript before submission.

Corresponding authors

Correspondence to Alba Silipo or Dianne K. Newman.

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PowerPoint slides

Glossary

Hopanoids

Pentacyclic lipids with C6 A-D rings and a C5 E ring, among which six core methyl groups are distributed. Hopanoids are also characterized by the formation of accessory groups at their C2, C3 and C30 positions.

Sterols

Tetracyclic lipids with C6 A-C rings and a C5 D ring. The parent compounds for all sterols contain oxygen groups at the C3 position.

Terpenoids

Molecules assembled from two or more C5 isoprene units that share the core formula (C5H8)n. They are also known as isoprenoids.

Triterpenoid

Molecules derived from assemblies of six isoprene units with the core formula (C5H8)6 or C30H48. They may be acyclic or cyclic.

Squalene

An acyclic triterpene with an irregular (tail-to-tail) linkage between two 3-isoprene units; a parent molecule of cyclic triterpenoids.

Triterpenoid cyclase

A superfamily of enzymes that convert acyclic triterpenoids, including squalene and 2,3-oxidosqualene, into various cyclic products.

Oxidosqualene cyclases

(OSCs). A family of predominantly eukaryotic 3-β-hydroxytriterpene cyclases that transform 2,3-oxidosqualene into sterols and diverse other cyclic triterpenoids.

Squalene-hopene cyclases

A family of predominantly bacterial 3-deoxytriterpene cyclases that cyclize squalene to primarily form hopanoids.

C30 hopanoids

Short hopanoids containing no additional carbon atoms that are not derived from squalene.

Tetrahymanol

A hopanoid-like compound with a C6 E-ring. In bacteria, it is made from E-ring expansion of the C30 hopanoid diploptene.

Legume

Legumes are flowering plants of the Fabaceae (previously known as Leguminosae) family, which includes economically important crops such as soybeans, common beans and peanuts.

C35 hopanoids

Extended hopanoids that contain ribose-derived hydrocarbon side chains at their C30 position.

2-Methyl-hopanoids

(2Me-hopanoids). Hopanoids containing an accessory methyl group at the C2 position.

3-Methyl-hopanoids

(3Me-hopanoids). Hopanoids containing an accessory methyl group at the C3 position.

Liposomes

Spherical vesicles surrounded by one or more lipid bilayers that can be produced from cellular membranes in vivo or synthetically by sonication or extrusion of lipids into aqueous solution.

Bacteriohopanetetrol

(BHT). A common C35 hopanoid containing a tetra-hydroxylated C5 side chain.

Membrane fluidity

The rotational and diffusional freedom of movement of molecules within a membrane.

Lipid rafts

Membrane microdomains with high stability that are thought to recruit specific membrane-associated proteins to spatially regulate their functions.

Lipopolysaccharides

(LPSs). Complex, heat-stable amphiphilic lipids that are the main component of the external leaflet of the outer membrane of Gram-negative bacteria.

Lipid A

The lipophilic moiety of lipopolysaccharides.

Hypoxic

An environment with a low concentration of oxygen (usually less than 30% saturation).

Nitrogen fixation

The conversion of dinitrogen gas into fixed or bioavailable nitrogen sources such as ammonia.

Nitrogenase

A bacterial enzyme complex that performs the following reaction: N2 + 16ATP + 10H+ + 8e → 2NH4+ + H2 + 16ADP−Pi

Root nodule

A specialized root organ that is generated by most legume plants to house nitrogen-fixing symbionts and create a specialized microenvironment to support bacterial nitrogen fixation.

Rhizobia

A paraphyletic group of nitrogen-fixing soil bacteria that can engage in symbioses with legumes.

Leghaemoglobin

An oxygen-carrying haem protein expressed in the root nodules of rhizobial host plants.

Aeschynomene

A genus of tropical legumes that is broadly distributed globally and is used for livestock grazing.

Hopanoid-lipid A

(HoLa). An extended hopanoid that is covalently attached to lipid A and appears to be unique to the Bradyrhizobiaceae.

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Belin, B., Busset, N., Giraud, E. et al. Hopanoid lipids: from membranes to plant–bacteria interactions. Nat Rev Microbiol 16, 304–315 (2018). https://doi.org/10.1038/nrmicro.2017.173

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