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Rhamnose
Rhamnose
Rhamnose
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Rhamnose[1]
Names
IUPAC name
6-Deoxy-L-mannopyranose
Systematic IUPAC name
(2R,3R,4R,5R,6S)-6-Methyloxane-2,3,4,5-tetrol
Other names
Isodulcit
α-L-Rhamnose
L-Rhamnose
L-Mannomethylose
α-L-Rha
α-L-Rhamnoside
α-L-Mannomethylose
6-Deoxy-L-mannose
L-Rhamnopyranose
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
DrugBank
ECHA InfoCard 100.020.722 Edit this at Wikidata
KEGG
UNII
  • InChI=1S/C6H12O5/c1-3(8)5(10)6(11)4(9)2-7/h2-6,8-11H,1H3/t3-,4-,5-,6-/m0/s1 checkY
    Key: PNNNRSAQSRJVSB-BXKVDMCESA-N checkY
  • InChI=1/C6H12O5/c1-3(8)5(10)6(11)4(9)2-7/h2-6,8-11H,1H3/t3-,4-,5-,6-/m0/s1
    Key: PNNNRSAQSRJVSB-BXKVDMCEBH
  • O=C[C@H](O)[C@H](O)[C@@H](O)[C@@H](O)C
Properties
C6H12O5
Molar mass 164.157 g·mol−1
Density 1.41 g/mL
Melting point 91 to 93 °C (196 to 199 °F; 364 to 366 K) (monohydrate)
−99.20·10−6 cm3/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

Rhamnose (Rha, Rham) is a naturally occurring deoxy sugar. It can be classified as either a methyl-pentose or a 6-deoxy-hexose. Rhamnose predominantly occurs in nature in its L-form as L-rhamnose (6-deoxy-L-mannose). This is unusual, since most of the naturally occurring sugars are in D-form. Exceptions are the methyl pentoses L-fucose and L-rhamnose and the pentose L-arabinose. However, examples of naturally occurring D-rhamnose are found in some species of bacteria, such as Pseudomonas aeruginosa and Helicobacter pylori.[2]

Rhamnose can be isolated from buckthorn (Rhamnus), poison sumac, and plants in the genus Uncaria. Rhamnose is also produced by microalgae belonging to class Bacillariophyceae (diatoms).[3]

Rhamnose is commonly bound to other sugars in nature. It is a common glycone component of glycosides from many plants. Rhamnose is also a component of the outer cell membrane of acid-fast bacteria in the Mycobacterium genus, which includes the organism that causes tuberculosis.[4] Natural antibodies against L-rhamnose are present in human serum,[5] and the majority of people seem to possess IgM, IgG or both of these types of immunoglobulins capable of binding this glycan.[6]

An interesting particularity of rhamnose is the presence of formaldehyde production when reacted with periodates in the vicinal diol cleavage reaction, that makes it very useful to remove excess periodate in glycerol or other vicinal diol analysis, that would otherwise give colored blank issues.[7]

See also

[edit]

Disaccharides:

Polysaccharides:

Glycosides:

References

[edit]

Further reading

[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Rhamnose

View on Grokipedia
from Grokipedia
Rhamnose is a naturally occurring classified as a 6-deoxy-L-mannose or methylpentose, with the molecular formula C₆H₁₂O₅ and a structure featuring hydroxyl groups at positions 2, 3, and 4, and a at position 5 of the backbone. It exists primarily in the L-configuration in and is essential for the structural integrity of bacterial cell walls and plant . In biological systems, rhamnose is a critical component of lipopolysaccharides (LPS) in , such as and , where it contributes to outer membrane stability and pathogenicity. It also forms part of rhamnogalacturonan I in plant cell walls, comprising 20–35% of , aiding in structural support and cell adhesion. of rhamnose typically occurs via the dTDP-rhamnose pathway in , involving four enzymes—RmlA (glucose-1-phosphate thymidylyltransferase), RmlB (4,6-dehydratase), RmlC (3,5-epimerase), and RmlD (reductase)—which convert dTDP-glucose to dTDP-L-rhamnose for incorporation into glycoconjugates. Alternative pathways, such as UDP-rhamnose in fungi and plants, enable its production in non-bacterial organisms. Due to its absence in mammals, rhamnose-containing compounds have garnered attention for therapeutic applications, including via rhamnose-modified nanoparticles that exploit bacterial-specific recognition for antibacterial agents. In , rhamnose conjugation enhances vaccine efficacy against tumors by recruiting natural antibodies and boosting T-cell responses, as seen in conjugates with tumor-associated carbohydrate antigens like MUC1. Additionally, rhamnolipids—biosurfactants produced by bacteria like —demonstrate selective cytotoxicity against cancer cells, such as breast carcinoma lines, with IC₅₀ values of approximately 8–30 μg/mL.

Structure and nomenclature

Chemical structure

Rhamnose has the molecular formula \ceC6H12O5\ce{C6H12O5} and a monoisotopic of 164.068473 Da. Its composition consists of six carbon atoms, twelve atoms, and five oxygen atoms. This is classified as a 6-deoxy-hexose or, equivalently, a -pentose due to the replacement of the at C6 with a relative to typical hexoses. The naturally occurring form, L-rhamnose, is specifically 6-deoxy-L-mannose, sharing the stereochemical configuration of L-mannose at carbons 2 through 5 but lacking the oxygen at C6. In its open-chain form, L-rhamnose is an with an group at C1 and hydroxyl groups at C2, C3, C4, and C5. The L-configuration is evident in its , which depicts the chiral centers as follows: \ceCHO∣\ceH−C−OH∣\ceH−C−OH∣\ceHO−C−H∣\ceHO−C−H∣\ceCH3\begin{array}{c} \ce{CHO} \\ | \\ \ce{H-C-OH} \\ | \\ \ce{H-C-OH} \\ | \\ \ce{HO-C-H} \\ | \\ \ce{HO-C-H} \\ | \\ \ce{CH3} \end{array} In , L-rhamnose predominantly exists in s, with the (six-membered ring) being the most stable, though minor (five-membered ring) tautomers are possible. The α-L-rhamnopyranose form, for example, features a chair-conformation ring with trans hydroxyl groups at C2 and C3, and the anomeric hydroxyl at C1 in the axial position, alongside the equatorial methyl at C5.

and stereoisomers

Rhamnose, specifically L-rhamnose, is systematically named as 6-deoxy-L-, reflecting its structural relation to mannose with a deoxy group at the C6 position. Alternative names include isodulcit, an older designation, and L-rhamnopyranose for its common . The term "rhamnose" originates from the New Latin genus name Rhamnus, referring to buckthorn plants from which it was first isolated in the . As a , rhamnose features four chiral centers at C2, C3, C4, and C5 in its open-chain form, theoretically allowing for 16 stereoisomers. In nature, it predominantly occurs in the L-series configuration as L-rhamnose (6-deoxy-L-mannose), which is biologically significant in various . The , D-rhamnose (6-deoxy-D-mannose), is rare and primarily noted in specific bacterial contexts, such as in Pseudomonas aeruginosa. L-rhamnose and L-fucose are both common 6-deoxy-L-hexoses found in nature, with L-fucose being the 6-deoxy derivative of L-galactose. Like other , L-rhamnose exists in equilibrium between its open-chain and cyclic forms, primarily as α-L-rhamnopyranose and β-L-rhamnopyranose anomers in .

Physical properties

Appearance and solubility

Rhamnose is typically observed as a crystalline solid at , presenting as a fine powder that is odorless and possesses a mildly sweet . The α-L-rhamnose monohydrate form melts at approximately 91–93 °C, while the anhydrous form exhibits a higher around 122 °C. This low melting point for the monohydrate reflects its hydrated crystalline . Rhamnose demonstrates high in , dissolving up to 300 g/L (equivalent to 30 g/100 mL) at 20 °C, owing to its polar hydroxyl groups enhanced by the deoxy configuration at C6, which maintains sufficient hydrophilicity. It is also soluble in polar organic solvents such as (approximately 36 mg/mL) and , but remains insoluble in non-polar solvents like . As a , rhamnose is hygroscopic, particularly in its β-form, which readily absorbs moisture from the air and may convert to the α-form under humid conditions. In solid form, it remains chemically stable under standard ambient conditions, with no significant when stored properly in a dry environment.

Rhamnose, as a chiral deoxyhexose, exhibits optical activity primarily through its interaction with plane-polarized light, quantified by , which varies with its anomeric configuration. For the naturally occurring L-rhamnose, the equilibrium in at 20°C is +8.9° after . The pure α-L-rhamnose displays an initial specific rotation of [α]D20 = -7.7° (c = 10), while the β-L-rhamnose starts at +31.5° (c = 10, measured 1 minute after dissolution), both converging to the equilibrium value over time due to anomerization in . The observed specific rotation of rhamnose is influenced by several factors, including solution concentration (as it is defined per unit concentration), (with typical measurements at 20°C), and the medium, which can alter the equilibrium between α and β forms. These variations in provide a means to monitor kinetics and confirm the stereochemical integrity of rhamnose samples, tying directly to its defined L-configuration at multiple chiral centers. In the ultraviolet-visible range, rhamnose shows negligible absorption above 210 nm owing to the absence of conjugated chromophores or aromatic systems; weak end absorption occurs below this wavelength from n→σ* transitions involving oxygen atoms, enabling limited direct UV detection in analytical methods for carbohydrates. Infrared (IR) spectroscopy offers distinctive signatures for rhamnose identification, featuring a broad O-H stretching band at ~3400 cm⁻¹ due to hydrogen bonding among hydroxyl groups, symmetric and asymmetric C-H stretches at ~2900 cm⁻¹ and ~2950 cm⁻¹ from the methyl and methylene groups, and intense C-O stretching vibrations in the 1000–1150 cm⁻¹ "fingerprint" region characteristic of rings. Nuclear magnetic resonance (NMR) serves as a primary tool for structural confirmation of rhamnose, revealing key proton and carbon signals. In 1H (D2O), the C-6 methyl protons appear as a doublet at δ ≈ 1.25 ppm (J ≈ 6.5 Hz), the anomeric H-1 at δ 4.8–5.2 ppm (distinguishing α from β via constants), and other ring protons between 3.2–4.2 ppm. Corresponding 13C shifts include the anomeric C-1 at δ ≈ 100–102 ppm, the deoxy methyl C-6 at δ ≈ 18 ppm, and oxygenated carbons at 70–85 ppm, facilitating unambiguous assignment in mixtures.

Chemical properties

Reactivity and stability

Rhamnose functions as a due to the presence of a free anomeric carbon, which enables equilibrium between its cyclic forms and the open-chain structure. This property allows it to participate in redox reactions and undergo in aqueous solutions, where the changes from an initial value, such as [α]D20 = -7.7° for the α-anomer, to an equilibrium value of +8.9°. As a , rhamnose also engages in the , a non-enzymatic browning process involving condensation with amino groups to form advanced glycation end products, as demonstrated in studies with leading to specific heterocyclic compounds. Under neutral conditions, rhamnose exhibits good stability in aqueous media, maintaining its structure during without significant decomposition, which supports its use in biochemical and analytical applications. However, it is sensitive to oxidation by agents such as (VI) in acidic environments, involving chromic formation at the primary hydroxyl group and oxidation to L-1,4-rhamnonolactone without C-C bond cleavage. In strong acids or bases, rhamnose can undergo or further breakdown, though its C-C bonds provide relative resistance to complete acid compared to ether-linked . The pKa of its most acidic proton, associated with the anomeric hydroxyl, is approximately 12.3, indicating low acidity and the absence of strongly acidic groups like those in uronic acids. The hydroxyl groups at positions 2, 3, and 4 of rhamnose are reactive sites for esterification, enabling the formation of esters with fatty acids via enzymatic or chemical methods, which alters its and . Additionally, the anomeric position supports reactions, where rhamnose acts as a donor in the synthesis of rhamnosides, often achieving β-L-rhamnosylation through specialized catalysts to control . The deoxy configuration at C6 somewhat diminishes its overall reactivity toward certain oxidants relative to fully hydroxylated hexoses like .

Common derivatives

Rhamnose serves as a key component in various nucleotide-activated forms that facilitate its incorporation into glycoconjugates. UDP-L-rhamnose is the primary activated form in plants, while GDP-L-rhamnose is used in fungi, enabling the transfer of L-rhamnose residues during glycosylation reactions. In bacteria, dTDP-L-rhamnose predominates as the sugar donor for synthesizing cell wall polysaccharides and lipopolysaccharides, synthesized from dTDP-D-glucose through a series of enzymatic dehydrations and reductions. These nucleotide sugars are essential for the biosynthesis of complex carbohydrates, with dTDP-L-rhamnose being particularly critical for mycobacterial growth and virulence. Rhamnose frequently appears as a glycoside in natural products, particularly in rhamnosides linked to and . In , such as (quercetin-3-O-rutinoside), L-rhamnose is attached via an α-1,6 linkage to a glucose moiety, enhancing the compound's and . , abundant in plants like and , exemplifies how rhamnosylation modulates properties for and applications. , amphiphilic glycosides found in many plant species, often incorporate rhamnose in their sugar chains, contributing to their surfactant-like and hemolytic activities; for instance, in feature rhamnosyl units. Beyond simple glycosides, rhamnose forms notable derivatives in and polymers. Rhamnolipids, biosurfactants produced mainly by , consist of one or two L-rhamnose units β-glycosidically linked to β-hydroxylated chains, exhibiting low and high biodegradability for applications in and . Methyl α-L-rhamnopyranoside, a protected form of rhamnose, is commonly used as a synthetic intermediate in carbohydrate chemistry due to its stability and ease of manipulation. In polymeric contexts, rhamnogalacturonan I (RG-I), a major domain in plant s, features an alternating backbone of L-rhamnose and D-galacturonic acid, with neutral side chains that influence cell wall porosity and plant growth. Derivatives of rhamnose are synthesized via enzymatic or chemical methods to produce these modified forms for research and industrial use. Enzymatic approaches, such as reverse using α-L-rhamnosidases or multi-enzyme cascades with thymidylyltransferases, enable regioselective and activation, as seen in the one-pot production of dTDP-L-rhamnose from glucose precursors. Chemical synthesis involves strategies and coupling reactions, for example, forming methyl rhamnosides through acid-catalyzed methanolysis of rhamnose, providing scalable routes for and analogs.

Natural occurrence

In plants

L-Rhamnose is a common component of plant cell walls, where it contributes to the structure of pectic . It is particularly abundant in rhamnogalacturonan I (RG-I), forming the galacturonic acid-rhamnose backbone and comprising 20–35% of , which provides and aids in . Rhamnose is also present in rhamnogalacturonan II (RG-II), a complex pectin domain involved in cell wall integrity, as well as in seed mucilage and flavonol glycosides, where it influences and stress responses.

In bacteria and other organisms

In , rhamnose serves as a key component of cell surface structures, particularly in lipopolysaccharides (LPS) and cell wall polysaccharides, contributing to structural integrity and interactions with host environments. In such as , L-rhamnose is a major constituent of the O-antigen portion of LPS, forming repeating units that include rhamnose, , and , which are essential for the polysaccharide's repeating backbone. For instance, in Salmonella Typhimurium serogroup B, the O-antigen 4,5,12 includes L-rhamnose in its saccharide backbone, influencing the antigen's stability and serological specificity. These rhamnose-containing O-antigens are biosynthesized via dedicated pathways and exported to the outer membrane, where they modulate bacterial and immune evasion. In , rhamnose is prominently featured in wall teichoic acids and , which anchor to and extend into the matrix. For example, in streptococci like , the is richly decorated with rhamnose-glucose (RGP), consisting of a polyrhamnose backbone substituted with glucose residues, which are critical for and structural organization. Similarly, rhamnose-rich (Rha-CWPS) are widespread in ovoid-shaped , including such as species, where they form a polyrhamnose core (rhamnan) with variable side-chain substituents like glucose or , aiding in and interactions with the environment. In pathogenic like , L-rhamnose is an essential component of the , linking mycolic acids to and supporting the integrity of the outer envelope, with dTDP-rhamnose serving as the activated donor for its incorporation. In fungi, L-rhamnose occurs as a minor but notable component of glycans and glycoproteins, contributing to structural and host-pathogen interactions in species such as and . It has been detected in the cell walls of various fungi, including , Madurella, , and , often playing roles in virulence and environmental adaptation. Beyond prokaryotes and fungi, rhamnose occurs only in trace amounts in other eukaryotes, particularly in non-mammalian animals, and is notably absent as a free in mammals. It detected in minor quantities within certain animal glycosaminoglycans, such as those derived from sources like , where rhamnose contributes to sulfated structures with potential bioactive roles. In mammals, while free rhamnose is not present, trace L-rhamnose identified in specific glycoproteins, including those from skin extracts, marking it as a rare constituent possibly acquired from microbial sources or minor endogenous pathways. These limited occurrences highlight rhamnose's primary association with microbial systems rather than higher eukaryotes. Evolutionarily, rhamnose biosynthesis and incorporation into cell surface structures appear clade-specific within bacteria, often linked to enhanced virulence in pathogenic lineages. For instance, in plant and animal pathogens like Xanthomonas species and Streptococcus groups, rhamnose-rich polysaccharides promote adhesion, biofilm formation, and resistance to host defenses, suggesting adaptive selection for these traits in specific bacterial clades. This clade-specific distribution underscores rhamnose's role in diversifying bacterial surface architectures for niche-specific survival and pathogenicity.

Biosynthesis

In plants

In plants, L-rhamnose is biosynthesized as UDP-L-rhamnose (UDP-Rha) primarily in the through a three-step enzymatic pathway starting from UDP-D-glucose (UDP-Glc). The process begins with the of UDP-Glc to form UDP-4-keto-6-deoxy-D-glucose (UDP-4K6DG) catalyzed by a 4,6-dehydratase activity. This intermediate then undergoes 3,5-epimerization to UDP-4-keto-L-rhamnose (UDP-4KR), followed by 4-keto reduction to yield UDP-Rha. The pathway requires NAD⁺ as a cofactor for the dehydratase step and NADPH for the reductase step, with UTP serving as the energy source for initial activation of glucose to UDP-Glc. Key enzymes in this pathway are the plant-specific rhamnose synthases RHM1 and RHM2 (also known as MUM4), which are multidomain proteins exhibiting trifunctional activity. RHM2, for instance, consists of an N-terminal dehydratase domain (residues 1–370) and a C-terminal domain (residues 371–667) that combines epimerase and reductase functions, enabling the complete conversion of UDP-Glc to UDP-Rha in a single polypeptide. These enzymes are localized in the , and the resulting UDP-Rha is subsequently transported into the Golgi apparatus via specific nucleotide-sugar transporters such as URGT1 and URGT2 for incorporation into . The biosynthesis of UDP-Rha is transcriptionally regulated, with RHM1 expression upregulated in growing tissues such as roots and young cotyledons to meet demands for cell wall expansion. Mutations in these genes lead to significant cell wall defects; for example, Arabidopsis rhm1 mutants exhibit reduced UDP-Rha pools, resulting in altered flavonol glycosylation and compensatory changes in cell wall composition that suppress certain root hair defects but cause overall helical growth phenotypes. Similarly, rhm2/mum4 mutants display abolished enzymatic activity, leading to decreased rhamnogalacturonan I (RG-I) levels and defective seed mucilage extrusion. This pathway supplies rhamnose residues essential for pectic polymers like RG-I in plant cell walls.

In bacteria

In , L-rhamnose is biosynthesized as the activated nucleotide sugar dTDP-L-rhamnose via a dedicated four-enzyme pathway starting from D-glucose-1-phosphate (Glc-1-P). The pathway initiates with RmlA (glucose-1-phosphate thymidylyltransferase), which catalyzes the reversible reaction of Glc-1-P with dTTP to form dTDP-D-glucose and . This is followed by RmlB (NAD+-dependent 4,6-dehydratase), which dehydrates dTDP-D-glucose to dTDP-4-keto-6-deoxy-D-glucose. RmlC (3,5-epimerase) then performs epimerization to yield dTDP-4-keto-6-deoxy-L-mannose, and finally, RmlD (NADPH-dependent 4-ketoreductase) reduces the 4-keto group to produce dTDP-L-rhamnose. The genes encoding these enzymes (rmlA–D) are commonly clustered within the rfb locus in Gram-negative pathogens, where they play a critical role in synthesizing rhamnose-containing O-antigens of (LPS). This clustering facilitates coordinated expression essential for LPS assembly, which is vital for bacterial outer integrity and . Pathway variations occur in like streptococci, which produce dTDP-L-rhamnose for rhamnose-rich cell wall polysaccharides, and in mycobacteria, where it contributes to and lipoarabinomannan structures. The RmlC enzyme is a key target for development, as inhibitors such as Ri03 disrupt rhamnose biosynthesis and impair viability in streptococci and mycobacteria. Recombinant expression of bacterial rmlA–D genes in enables efficient one-pot production of dTDP-L-rhamnose, with optimized systems achieving yields of up to 65% from Glc-1-P and dTTP substrates under mild conditions (pH 8.5, 30°C).

Biological roles

Structural functions

In plant cell walls, rhamnose serves as a critical component of pectins, particularly forming the backbone of rhamnogalacturonan I (RG-I) alongside galacturonic acid, which imparts flexibility to the structure by introducing that allow for cell elongation and accommodation of growth. This flexibility is essential for maintaining in the cell wall matrix, enabling the diffusion of water, nutrients, and signaling molecules while preventing excessive rigidity that could hinder expansion. Side chains attached to rhamnose residues in RG-I further modulate these properties, contributing to the overall biomechanical resilience of primary and secondary walls. In bacterial envelopes, rhamnose stabilizes the outer membrane of through its integration into (LPS), where it forms part of the O-antigen that reinforces membrane integrity and impermeability. In , such as cocci in the genera Lactococcus and , rhamnose constitutes rhamnan polymers within cell wall and teichoic acids, which anchor the layer and maintain spherical cell shape during division and environmental stress. These rhamnose-rich structures provide a that supports wall rigidity and prevents deformation. The 6-deoxy configuration of rhamnose, lacking a hydroxyl group at the C6 position, reduces the overall hydrophilicity of the compared to fully hydroxylated sugars like , promoting denser molecular packing and enhanced structural rigidity in cell walls. This physicochemical property aids in forming compact, stable architectures that withstand mechanical forces. Evidence from mutants underscores rhamnose's structural importance; in plants, disruptions in , such as in rhm1 mutants, cause cell expansion defects and brittle walls due to compromised RG-I integrity, leading to reduced flexibility and increased fragility. Similarly, bacterial rhamnose-deficient mutants, like those in , display severe morphological alterations, cell division failures, and lysis from weakened envelopes, confirming rhamnose's role in preventing structural collapse.

Signaling and metabolic roles

In plants, rhamnose plays key roles in modulating signaling through its incorporation into rhamnosylated , which influence homeostasis and thereby affect developmental processes such as and shoot growth. Specifically, 7-rhamnosylated forms of like and alter transport and distribution by interacting with auxin efflux carriers, leading to changes in architecture and stress responses. Additionally, rhamnose within rhamnogalacturonan-II (RG-II), a component of the , is essential for growth and fertilization; mutants defective in RG-II biosynthesis exhibit impaired elongation due to altered integrity at the tube tip. Rhamnose-containing pectins also contribute to resistance by reinforcing barriers and facilitating the release of damage-associated molecular patterns (DAMPs) that trigger immune signaling upon . In , rhamnose serves as a in (LPS) O-antigens, enabling host immune evasion; for instance, in the plant pathogen , a rhamnose-rich O-antigen promotes to vessels and suppresses host defenses, enhancing colonization and disease progression. Furthermore, rhamnolipids—rhamnose-conjugated biosurfactants produced by —are regulated by systems like Las and Rhl, facilitating formation and dispersal to optimize and survival in host environments. Metabolically, rhamnose integrates into broader pathways as a precursor for glycosylating , where UDP-L-rhamnose donates the sugar moiety to flavonol aglycones, enhancing their stability, solubility, and bioactivity in . In catabolic processes, particularly in and fungi, L-rhamnose undergoes to L-rhamnulose-1-phosphate, followed by cleavage via an aldolase to (DHAP) and L-lactaldehyde; the latter is oxidized to L-lactate, while DHAP enters , ultimately yielding and other products under anaerobic conditions. Emerging research highlights rhamnose's potential in non-mammalian interactions, where microbiota-derived rhamnose modulates bacterial-macrophage responses by enhancing and alleviating proinflammatory production during infections. In gut symbionts like Bacteroides thetaiotaomicron, rhamnose metabolism supports tolerance, influencing microbial community dynamics and host-microbe .

Applications

Industrial production

L-Rhamnose is primarily produced industrially through extraction from natural plant and algal sources via acid or enzymatic of rhamnose-containing glycosides and . A key method involves hydrolyzing from peels, such as grapefruit (Citrus paradisi), using engineered strains of the filamentous fungus with disrupted rhamnose catabolism genes (rha1 and lra3); this consolidated bioprocess yields 1.73 g/L L-rhamnose from 122 g/L dry peel mass after 50 hours without pretreatment. Another approach utilizes the soapbark tree (Quillaja saponaria), where rhamnose is released by acid of glycosides extracted from the bark through aqueous processing, though this is often integrated into broader production for adjuvants like QS-21. From marine sources, crude ulvan from the green alga Ulva fasciata is hydrolyzed using reusable carbon-embedded sulfonated resins as catalysts under mild conditions (90–120 °C, 8–24 hours), achieving up to 85% L-rhamnose yield with high selectivity and no furanic byproducts, followed by as the monohydrate. Microbial fermentation offers an alternative for scalable production, particularly by leveraging bacteria that synthesize rhamnose as part of biosurfactants. Pseudomonas aeruginosa strains are cultured on carbon sources like to produce rhamnolipids (up to 50 g/L), which are then acid-hydrolyzed (e.g., with at 30–100 °C) to liberate L-rhamnose, yielding 15–24 g/L after separation via extraction or ion-exchange . Engineered overexpressing the rmlABCD for dTDP-L-rhamnose has been developed as a biocatalyst, though direct free L-rhamnose release requires additional steps. Chemical and enzymatic syntheses provide routes for high-purity production, often starting from abundant sugars. L-Rhamnose (6-deoxy-L-mannose) can be synthesized from L-mannose via selective deoxy reduction at the C6 position, though these are less common industrially due to cost. Enzymatic methods employ rare sugar isomerases, such as L-rhamnose isomerase variants, to interconvert deoxyhexoses, enabling production from precursors like L-rhamnulose with conversions up to 44% at 25 g/L substrate. Commercially, L-rhamnose is available as L-rhamnose monohydrate with >98% purity (HPLC), supplied in bulk for applications in flavors and pharmaceuticals; its status as a rare contributes to higher production costs compared to common monosaccharides, limiting scale to specialized manufacturers.

Research and pharmaceutical uses

Rhamnose, recognized as a rare , has garnered interest in functional foods due to its potential as a low-calorie . Studies have demonstrated that L-rhamnose acts as a nonnutritive that promotes adipose and energy expenditure, offering benefits for management without significant caloric contribution. It serves as a natural flavor enhancer in products like and beverages, providing a lower-calorie alternative to traditional sugars while supporting prebiotic effects in the gut. Additionally, rhamnose-derived rhamnolipids exhibit potent anti-biofilm properties, disrupting microbial biofilms by altering integrity and inhibiting adhesion, which holds promise for preventing infections in pharmaceutical and medical device applications. In pharmaceutical contexts, rhamnose pathways in represent attractive targets for novel antibiotics, as inhibiting enzymes like RmlA in the dTDP-L-rhamnose pathway impairs formation and virulence in pathogens such as and species. For instance, allosteric inhibitors of glucose-1-phosphate thymidylyltransferase (RmlA) have shown bactericidal effects against , resensitizing resistant strains to existing β-lactam antibiotics. Rhamnose conjugates also enhance efficacy as adjuvants; monophosphoryl lipid A-rhamnose derivatives stimulate robust responses against protein and antigens, outperforming unmodified adjuvants in promoting IgG production for tumor-associated targets like sTn. Rhamnose serves as a key tool in glycobiology research through specific that detect and bind rhamnose residues on glycans, enabling studies of carbohydrate-protein interactions in microbial and host systems. Multivalent rhamnose-binding , such as those from marine bivalves, facilitate high-affinity recognition for detection and inhibition, with applications in probing cell surface glycans. In plant studies, metabolic labeling with rhamnose analogs allows visualization of rhamnogalacturonan-II incorporation into cell walls via , revealing dynamic assembly during growth and stress responses. Emerging applications include rhamnose-binding probes for cancer imaging, where fluorine-18-labeled L-rhamnose derivatives enable PET tracing of rhamnose-utilizing pathogens in tumor microenvironments, potentially aiding infection-associated cancer diagnostics. Folic acid-rhamnose conjugates target receptor-overexpressing cancer cells, recruiting antibodies for selective imaging and therapy. In the , advances in have leveraged bacterial rhamnosyltransferases to engineer custom rhamnosides, enabling efficient biocatalytic synthesis of bioactive glycoconjugates for and design.

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