Specific hydroxylation and glucuronidation of 2'-hydroxyflavanone by Streptomyces coeruleorubidus NRRL B-2569.

Flavonoids constitute a class of natural compounds with varied bioactivities. Nevertheless, the potential health benefits of flavonoids for humans are often compromised by their low water solubility and limited bioavailability. In this study, four derivatives, namely 2',5'-dihydroxyflavanone (2), 5'-dihydroxyflavone-2'-O-β-d-glucuronide (3), and two isomers of hydroxyflavanone-2'-O-β-d-glucuronide (4 and 5), were biosynthesized from substrate 2'-hydroxyflavanone (1) through the specific hydroxylation and glucuronidation using Streptomyces coeruleorubidus NRRL B-2569.

Enhancing the physicochemical properties and bioactivities of 2'-hydroxyflavanone through fungal biotransformation.

Flavonoids comprise a group of natural compounds with diverse bioactivities; however, their low water solubility and limited bioavailability often impede their potential health benefits for humans. In this study, five derivatives, namely 2',5'-dihydroxyflavanone (1), 2'-dihydroxyflavanone-5'-O-4″-O-methyl-β-d-glucoside (2), 2'-dihydroxyflavanone-6-O-4″-O-methyl-β-d-glucoside (3), 2'-dihydroxyflavanone-3'-O-4″-O-methyl-β-d-glucoside (4) and hydroxyflavanone-2'-O-4″-O-methyl-β-d-glucoside (5), were biosynthesized from 2'-hydroxyflavanone through microbial transformation using Beauveria bassiana ATCC 7159. Product 1 was identified as a known compound while 2-5 were structurally characterized as new structures through extensive 1D and 2D NMR analysis.

Sustained silencing peanut allergy by xanthopurpurin is associated with suppression of peripheral and bone marrow IgE-producing B cell.

Introduction: Peanut allergy is an immunoglobulin E (IgE) mediated food allergy. L. (), a Chinese herbal medicine, protects against peanut-induced anaphylaxis by suppressing IgE production .

Microbial glycosylation of antitubercular agent chlorflavonin.

Flavonoids have shown health-benefiting properties, such as antioxidative and anti-inflammatory activities, and are commonly used as nutraceuticals and pharmaceuticals. Although flavonoids are predominantly identified from plants, several filamentous fungal species have also been reported to produce bioactive flavonoids, including chlorflavonin from Aspergillus candidus, a novel halogenated flavonoid with potent antifungal and antitubercular (anti-TB) activities. Unfortunately, the low water-solubility of this molecule may hinder its bioavailability.

Berberine-containing natural-medicine with boiled peanut-OIT induces sustained peanut-tolerance associated with distinct microbiota signature.

Background: Gut microbiota influence food allergy. We showed that the natural compound berberine reduces IgE and others reported that BBR alters gut microbiota implying a potential role for microbiota changes in BBR function.

Objective: We sought to evaluate an oral Berberine-containing natural medicine with a boiled peanut oral immunotherapy (BNP) regimen as a treatment for food allergy using a murine model and to explore the correlation of treatment-induced changes in gut microbiota with therapeutic outcomes.

Engineered production of bioactive polyphenolic O-glycosides.

Polyphenolic compounds (such as quercetin and resveratrol) possess potential medicinal values due to their various bioactivities, but poor water solubility hinders their health benefits to humankind. Glycosylation is a well-known post-modification method to biosynthesize natural product glycosides with improved hydrophilicity. Glycosylation has profound effects on decreasing toxicity, increasing bioavailability and stability, together with changing bioactivity of polyphenolic compounds.

Inhibition of pathologic immunoglobulin E in food allergy by EBF-2 and active compound berberine associated with immunometabolism regulation.

Introduction: Food allergy is a significant public health problem with limited treatment options. As Food Allergy Herbal Formula 2 (FAHF-2) showed potential as a food allergy treatment, we further developed a purified version named EBF-2 and identified active compounds. We investigated the mechanisms of EBF-2 on IgE-mediated peanut (PN) allergy and its active compound, berberine, on IgE production.

Formononetin isolated from inhibits B cell-IgE production by regulating ER-stress transcription factor XBP-1.

Rationale: IgE plays an important pathologic role in most, if not all, allergic conditions. We previously showed that ASHMI (anti-asthma herbal medicine intervention) suppressed IgE production in murine models of asthma and in asthma subjects. However, the active compounds in ASHMI responsible for the IgE suppression are still unknown.

Genus : A review of its folk uses, phytochemistry and pharmacology.

The genus belongs to the Vitaceae family and contains over 100 species. This paper reviewed folk uses, chemical constituents, pharmacological activities, and clinical applications of the medicinal plants in the genus . In addition, the paper also discussed the current problems for the further studies.

Creating diverse glycosides of 2'-hydroxyflavone through microbial glycosylation.

Four new 2'-hydroxyflavone glycosides, namely hydroxyflavone-2'-O-β-D-glucuronide (1), hydroxyflavone-2'-O-α-L-rhamnoside (2), hydroxyflavone-2'-O-β-D-glucoside (3), and hydroxyflavone-2'-O-4″-O-methyl-β-D-glucoside (4), were biosynthesized through microbial glycosylation using Streptomyces coeruleorubidus NRRL B-2569, Streptomyces toxytricini NRRL 15443, Escherichia coli BL21(DE3)/pWZ8, and Beauveria bassiana ATCC 7159, respectively. Compounds 1-4 were structurally characterized through extensive analysis of 1D and 2D NMR spectroscopic data. The water solubility of glycosylated products 1-4 were enhanced by 7 to 15 times compared to the substrate 2'-hydroxyflavone.

Time-dependent dual beneficial modulation of interferon-γ, interleukin 5, and Treg cytokines in asthma patient peripheral blood mononuclear cells by ganoderic acid B.

Th2 cytokines play a dominant role in the pathogenesis of allergic asthma. Interferon gamma (IFN-γ), a Th1 cytokine, links to therapeutic mechanisms of allergic asthma. Interleukin (IL)-10, a regulatory cytokine, is involved in the induction of immune tolerance.

Identification of a novel glucuronyltransferase from Streptomyces chromofuscus ATCC 49982 for natural product glucuronidation.

Glycosylation is an effective way to increase the polarity of natural products. UDP-glucuronyltransferases (UGTs) are commonly observed and extensively studied in phase II drug metabolism. However, UGTs in microorganisms are not well studied, which hampered the utilization of this type of enzyme in microbial glucuronidation of natural products.

A highly versatile fungal glucosyltransferase for specific production of quercetin-7-O-β-D-glucoside and quercetin-3-O-β-D-glucoside in different hosts.

Glycosylation is an effective way to improve the water solubility of natural products. In this work, a novel glycosyltransferase gene (BbGT) was discovered from Beauveria bassiana ATCC 7159 and heterologously expressed in Escherichia coli. The purified enzyme was functionally characterized through in vitro enzymatic reactions as a UDP-glucosyltransferase, converting quercetin to five monoglucosylated and one diglucosylated products.

A Computational Metabolic Model for Engineered Production of Resveratrol in .

Although engineered microbial production of natural compounds provides a promising alternative method to plant production and extraction, the process can be inefficient and ineffective in terms of time and cost. To render microbial systems profitable and viable, the process must be optimized to produce as much product as possible. To this end, this work illustrates the construction of a new probabilistic computational model to simulate the microbial production of a well-known cardioprotective molecule, resveratrol, and the implementation of the model to enhance the yield of the product in .

Identification and Characterization of an Efficient Phenylalanine Ammonia-Lyase from Photorhabdus luminescens.

A putative aromatic amino acid ammonia-lyase gene (named Pl-pal) was discovered in Photorhabdus luminescens DSM 3368. BLAST and phylogenetic analyses predicted that this enzyme is a histidine ammonia-lyase, whereas sequence alignment suggested that it is more likely a phenylalanine ammonia-lyase (PAL). This gene was amplified from P.

Discovery of a novel analogue of FR901533 and the corresponding biosynthetic gene cluster from Streptosporangium roseum No. 79089.

FR901533 (1, also known as WS79089B), WS79089A (2), and WS79089C (3) are polycyclic aromatic natural products with promising inhibitory activity to endothelin-converting enzymes. In this work, we isolated five tridecaketide products from Streptosporangium roseum No. 79089, including 1-3, benaphthamycin (4) and a novel FR901533 analogue (5).

Characterization of two new aromatic amino acid lyases from actinomycetes for highly efficient production of p-coumaric acid.

p-Coumaric acid (p-CA) is a bioactive natural product and an important industrial material for pharmaceuticals and nutraceuticals. It can be synthesized from deamination of L-tyrosine by tyrosine ammonia lyase (TAL). In this work, we discovered two aromatic amino acid lyase genes, Sas-tal and Sts-tal, from Saccharothrix sp.

Efficient production of gamma-aminobutyric acid by engineered Saccharomyces cerevisiae with glutamate decarboxylases from Streptomyces.

Gamma-aminobutyric acid (GABA) is an industrially valuable natural product. This study was aimed to establish an efficient food-grade production process of GABA by engineering Saccharomyces cerevisiae that is generally recognized as safe (GRAS). GABA can be produced by catalytic decarboxylation of l-glutamate (l-Glu) by glutamate decarboxylase (GAD, EC4.

Discovery and engineering of an endophytic strain from for efficient production of zeaxanthin diglucoside.

Background: Endophytic microorganisms are a rich source of bioactive natural products. They are considered as promising biofertilizers and biocontrol agents due to their growth-promoting interactions with the host plants and their bioactive secondary metabolites that can help manage plant pathogens. Identification of new endophytes may lead to the discovery of novel molecules or provide new strains for production of valuable compounds.

Modified substrate specificity of a methyltransferase domain by protein insertion into an adenylation domain of the bassianolide synthetase.

Background: Creating designer molecules using a combination of select domains from polyketide synthases and/or nonribosomal peptide synthetases (NRPS) continues to be a synthetic goal. However, an incomplete understanding of how protein-protein interactions and dynamics affect each of the domain functions stands as a major obstacle in the field. Of particular interest is understanding the basis for a class of methyltransferase domains (MT) that are found embedded within the adenylation domain (A) of fungal NRPS systems instead of in an end-to-end architecture.

Identification of new glutamate decarboxylases from for efficient production of γ-aminobutyric acid in engineered .

Background: Gamma (γ)-Aminobutyric acid (GABA) as a bioactive compound is used extensively in functional foods, pharmaceuticals and agro-industry. It can be biosynthesized via decarboxylation of monosodium glutamate (MSG) or L-glutamic acid (L-Glu) by glutamate decarboxylase (GAD; EC4.1.

Improved production of antifungal angucycline Sch47554 by manipulating three regulatory genes in Streptomyces sp. SCC-2136.

Sch47554 and Sch47555 are two angucyclines with antifungal activities against various yeasts and dermatophytes from Streptomyces sp. SCC-2136. The sch gene cluster contains several putative regulatory genes.

An efficient process for co-production of γ-aminobutyric acid and probiotic cells.

This study was to establish an integrated process for the co-production of γ-aminobutyric acid (GABA) and live probiotics. Six probiotic bacteria were screened and ATCC 6051 showed the highest GABA-producing capacity. The optimal temperature and initial pH value for GABA production in were found to be 30 °C and 8.

Identification and heterologous reconstitution of a 5-alk(en)ylresorcinol synthase from endophytic fungus Shiraia sp. Slf14.

A new type III polyketide synthase gene (Ssars) was discovered from the genome of Shiraia sp. Slf14, an endophytic fungal strain from Huperzia serrata. The intron-free gene was cloned from the cDNA and ligated to two expression vectors pET28a and YEpADH2p-URA3 for expression in Escherichia coli BL21(DE3) and Saccharomyces cerevisiae BJ5464, respectively.