脂質代謝物の産生とアレルギー疾患の制御

The intestinal tract is the largest immunological organ, which is responsible for the first line of defense by preventing the invasion of pathogenic microorganism and neutralizing pathogenic materials such as toxin. Simultaneously, it does not respond to harmless or beneficial antigens such as foods and intestinal commensal bacteria. These harmonized immune responses are critical for the maintenance of intestinal homeostasis and hence disruption of the system would lead to the development of immune diseases such as inflammatory bowel disease and food allergy. Especially dietary lipids among the dietary components have been studied for a long time, and it is considered that dietary lipids are important factors for regulating the development of allergy and inflammation. As analytical techniques of lipid metabolites have been highly developed in recent years, it has become clear that some lipid metabolites derived from dietary oils have strong physiological functions including the control of allergic and inflammatory diseases. These findings are currently leading to the new methods for preventing and treating allergic and inflammatory diseases by using lipid metabolites. In this article, we introduce the control of allergic and inflammatory diseases by dietary lipids and its metabolites

Host- and Microbe-Dependent Dietary Lipid Metabolism in the Control of Allergy, Inflammation, and Immunity

The intestine is the largest immune organ in the body, provides the first line of defense against pathogens, and prevents excessive immune reactions to harmless or beneficial non-self-materials, such as food and intestinal bacteria. Allergic and inflammatory diseases in the intestine occur as a result of dysregulation of immunological homeostasis mediated by intestinal immunity. Several lines of evidence suggest that gut environmental factors, including nutrition and intestinal bacteria, play important roles in controlling host immune responses and maintaining homeostasis. Among nutritional factors, ω3 and ω6 essential polyunsaturated fatty acids (PUFAs) profoundly influence the host immune system. Recent advances in lipidomics technology have led to the identification of lipid mediators derived from ω3- and ω6-PUFAs. In particular, lipid metabolites from ω3-PUFAs (e.g., eicosapentaenoic acid and docosahexaenoic acid) have recently been shown to exert anti-allergic and anti-inflammatory responses; these metabolites include resolvins, protectins, and maresins. Furthermore, a new class of anti-allergic and anti-inflammatory lipid metabolites of 17,18-epoxyeicosatetraenoic acid has recently been identified in the control of allergic and inflammatory diseases in the gut and skin. Although these lipid metabolites were found to be endogenously generated in the host, accumulating evidence indicates that intestinal bacteria also participate in lipid metabolism and thus generate bioactive unique lipid mediators. In this review, we discuss the production machinery of lipid metabolites in the host and intestinal bacteria and the roles of these metabolites in the regulation of host immunity

A Gene Cluster for Biosynthesis of Mannosylerythritol Lipids Consisted of 4-O-β-D-Mannopyranosyl-(2R,3S)-Erythritol as the Sugar Moiety in a Basidiomycetous Yeast Pseudozyma tsukubaensis.

Mannosylerythritol lipids (MELs) belong to the glycolipid biosurfactants and are produced by various fungi. The basidiomycetous yeast Pseudozyma tsukubaensis produces diastereomer type of MEL-B, which contains 4-O-β-D-mannopyranosyl-(2R,3S)-erythritol (R-form) as the sugar moiety. In this respect it differs from conventional type of MELs, which contain 4-O-β-D-mannopyranosyl-(2S,3R)-erythritol (S-form) as the sugar moiety. While the biosynthetic gene cluster for conventional type of MELs has been previously identified in Ustilago maydis and Pseudozyma antarctica, the genetic basis for MEL biosynthesis in P. tsukubaensis is unknown. Here, we identified a gene cluster involved in MEL biosynthesis in P. tsukubaensis. Among these genes, PtEMT1, which encodes erythritol/mannose transferase, had greater than 69% identity with homologs from strains in the genera Ustilago, Melanopsichium, Sporisorium and Pseudozyma. However, phylogenetic analysis placed PtEMT1p in a separate clade from the other proteins. To investigate the function of PtEMT1, we introduced the gene into a P. antarctica mutant strain, ΔPaEMT1, which lacks MEL biosynthesis ability owing to the deletion of PaEMT1. Using NMR spectroscopy, we identified the biosynthetic product as MEL-A with altered sugar conformation. These results indicate that PtEMT1p catalyzes the sugar conformation of MELs. This is the first report of a gene cluster for the biosynthesis of diastereomer type of MEL

Biosynthetic ability of diverse basidiomycetous yeast strains to produce the natural antioxidant ergothioneine

Abstract Sixteen strains of basidiomycetous yeasts were evaluated for their capability to produce ergothioneine (EGT), an amino acid derivative with strong antioxidant activity. The cells were cultured in either two synthetic media or yeast mold (YM) medium for 72 h, after which cytosolic constituents were extracted from the cells with hot water. After analyzing the extracts via liquid chromatography-mass spectrometry (LC-MS), we found that all strains produced varying amounts of EGT. The EGT-producing strains, including Ustilago siamensis, Anthracocystis floculossa, Tridiomyces crassus, Ustilago shanxiensis, and Moesziomyces antarcticus, were subjected to flask cultivation in YM medium. U. siamensis CBS9960 produced the highest amount of EGT at 49.5 ± 7.0 mg/L after 120 h, followed by T. crassus at 30.9 ± 1.8 mg/L. U. siamensis was also cultured in a jar fermenter and produced slightly higher amounts of EGT than under flask cultivation. The effects of culture conditions, particularly the addition of precursor amino acids, on EGT production by the selected strains were also evaluated. U. siamensis showed a 1.5-fold increase in EGT production with the addition of histidine, while U. shanxiensis experienced a 1.8-fold increase in EGT production with the addition of methionine. These results suggest that basidiomycetous yeasts could serve an abundant source for natural EGT producers

Amino acid sequence alignment of the PtEMT1p from <i>P</i>. <i>tsukubaensis</i> NBRC1940 and nine homologous proteins.

<p>(I), (II) and (III) show low-identity regions I, II, and III, respectively. Identical residues are shown on a black background. GAC96558_P. hub: <i>Pseudozyma hubeiensis</i> SY62. XP_011389468_U. may: <i>Ustilago maydis</i> 521. CDR99457.1_S. sci: <i>Sporisorium scitamineum</i>. CBQ73522_S. rei: <i>Sporisorium reilianum</i> SRZ2. CDI53946_M. pen: <i>Melanopsichium pennsylvanicum</i> 4. CCF52717_U. hor: <i>Ustilago hordei</i>. ETS61959_P. aph: <i>Pseudozyma aphidis</i> DSM70725. GAK68006_P. ant: <i>Pseudozyma antarctica</i>. GAC75887_P. ant: <i>Pseudozyma antarctica</i> T-34. P. tsu: <i>Pseudozyma tsukubaensis</i> NBRC1940.</p

Chemical structure of MELs.

<p>(A) Conventional type of MELs. (B) Diastereomer type of MEL-B.</p

The plasmid maps of pUXV1_neo::PaEMT1 and pUXV1_neo::PtEMT1.

<p>The plasmid maps of pUXV1_neo::PaEMT1 and pUXV1_neo::PtEMT1.</p

Alcaligenes lipid A functions as a superior mucosal adjuvant to monophosphoryl lipid A via the recruitment and activation of CD11b+ dendritic cells in nasal tissue.

We previously demonstrated that Alcaligenes-derived lipid A (ALA), which is produced from an intestinal lymphoid tissue-resident commensal bacterium, is an effective adjuvant for inducing antigen-specific immune responses. To understand the immunologic characteristics of ALA as a vaccine adjuvant, we here compared the adjuvant activity of ALA with that of a licensed adjuvant (monophosphoryl lipid A, MPLA) in mice. Although the adjuvant activity of ALA was only slightly greater than that of MPLA for subcutaneous immunization, ALA induced significantly greater IgA antibody production than did MPLA during nasal immunization. Regarding the underlying mechanism, ALA increased and activated CD11b+ CD103- CD11c+ dendritic cells in the nasal tissue by stimulating chemokine responses. These findings revealed the superiority of ALA as a mucosal adjuvant due to the unique immunologic functions of ALA in nasal tissue

Gene clusters of MEL biosynthesis.

<p>Emt1: erythritol/mannose transferase; Mac1 and Mac2: acyl transferases; Mat1: acetyl transferase; Mmf1: putative transporter.</p