• Screening for inhibitors of mutacin synthesis in Streptococcus mutans using fluorescent reporter strains.

      Premnath, Priyanka; Reck, Michael; Wittstein, Kathrin; Stadler, Marc; Wagner-Döbler, Irene; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (BMC, 2018-03-27)
      Within the polymicrobial dental plaque biofilm, bacteria kill competitors by excreting mixtures of bacteriocins, resulting in improved fitness and survival. Inhibiting their bacteriocin synthesis might therefore be a useful strategy to eliminate specific pathogens. We used Streptococcus mutans, a highly acidogenic inhabitant of dental plaque, as a model and searched for natural products that reduced mutacin synthesis. To this end we fused the promoter of mutacin VI to the GFP+ gene and integrated the construct into the genome of S. mutans UA159 by single homologous recombination. The resulting reporter strain 423p - gfp + was used to screen 297 secondary metabolites from different sources, mainly myxobacteria and fungi, for their ability to reduce the fluorescence of the fully induced reporter strain by > 50% while growth was almost unaffected (> 90% of control). Seven compounds with different chemical structures and different modes of action were identified. Erinacine C was subsequently validated and shown to inhibit transcription of all three mutacins of S. mutans. The areas of the inhibition zones of the sensor strains S. sanguinis and Lactococcus lactis were reduced by 35% to 61% in comparison to controls in the presence of erinacine C, demonstrating that the amount of active mutacins in the culture supernatants of S. mutans was reduced. Erinacines are cyathane diterpenes that were extracted from cultures of the edible mushroom Hericium erinaceus. They have anti-inflammatory, antimicrobial and neuroprotective effects. For erinacine C, a new biological activity was found here. We demonstrate the successful development of a whole-cell fluorescent reporter for the screening of natural compounds and report that erinacine C suppresses mutacin synthesis in S. mutans without affecting cell viability.
    • Secondary metabolite biosynthetic diversity in the fungal family Hypoxylaceae and Xylaria hypoxylon.

      Kuhnert, E; Navarro-Muñoz, J C; Becker, K; Stadler, M; Collemare, J; Cox, R J; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Elsevier, 2021-08-26)
      To date little is known about the genetic background that drives the production and diversification of secondary metabolites in the Hypoxylaceae. With the recent availability of high-quality genome sequences for 13 representative species and one relative (Xylaria hypoxylon) we attempted to survey the diversity of biosynthetic pathways in these organisms to investigate their true potential as secondary metabolite producers. Manual search strategies based on the accumulated knowledge on biosynthesis in fungi enabled us to identify 783 biosynthetic pathways across 14 studied species, the majority of which were arranged in biosynthetic gene clusters (BGC). The similarity of BGCs was analysed with the BiG-SCAPE engine which organised the BGCs into 375 gene cluster families (GCF). Only ten GCFs were conserved across all of these fungi indicating that speciation is accompanied by changes in secondary metabolism. From the known compounds produced by the family members some can be directly correlated with identified BGCs which is highlighted herein by the azaphilone, dihydroxynaphthalene, tropolone, cytochalasan, terrequinone, terphenyl and brasilane pathways giving insights into the evolution and diversification of those compound classes. Vice versa, products of various BGCs can be predicted through homology analysis with known pathways from other fungi as shown for the identified ergot alkaloid, trigazaphilone, curvupallide, viridicatumtoxin and swainsonine BGCs. However, the majority of BGCs had no obvious links to known products from the Hypoxylaceae or other well-studied biosynthetic pathways from fungi. These findings highlight that the number of known compounds strongly underrepresents the biosynthetic potential in these fungi and that a tremendous number of unidentified secondary metabolites is still hidden. Moreover, with increasing numbers of genomes for further Hypoxylaceae species becoming available, the likelihood of revealing new biosynthetic pathways that encode new, potentially useful compounds will significantly improve. Reaching a better understanding of the biology of these producers, and further development of genetic methods for their manipulation, will be crucial to access their treasures.
    • Secondary metabolites of Phlebopus species from Northern Thailand

      Chuankid, Boontiya; Schrey, Hedda; Thongbai, Benjarong; Raspé, Olivier; Arnold, Norbert; Hyde, Kevin David; Stadler, Marc; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Springer.com, 2020-12-01)
      Submerged cultures of the edible mushrooms Phlebopus portentosus and Phlebopus spongiosus were screened for their secondary metabolites by HPLC-UV/Vis and HR-LC-ESI-MS. Two new compounds, 9′-hydroxyphenyl pulvinone (1), containing an unusual pulvinone structure, and phlebopyron (2), together with the seven known pigments, atromentic acid (3), xerocomic acid (4), variegatic acid (5), methyl atromentate (6), methyl isoxerocomate (7), methyl variegatate (8), and variegatorubin (9) were isolated from the cultures. Their structures were assigned on the basis of extensive 1D/2D NMR spectroscopic analyses, as well as HR-ESI-MS, and HR-ESI-MS/MS measurements. Furthermore, the isolated compounds were evaluated for their antimicrobial and cytotoxic properties. 9′-hydroxyphenyl pulvinone (1), xerocomic acid (4), and methyl variegatate (8) exhibited weak to moderate cytotoxic activities against several tumor cell lines. The present paper provides a comprehensive characterization of pigments from the class of pulvinic acids that are present in the basidiomes of many edible bolete species.
    • Sesquiterpenes from an Eastern African Medicinal Mushroom Belonging to the Genus Sanghuangporus.

      Cheng, Tian; Chepkirui, Clara; Decock, Cony; Matasyoh, Josphat Clement; Stadler, Marc; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (American Cemical Society (ACS), 2019-05-24)
      During the course of searching for new anti-infective and other biologically active secondary metabolites from Kenyan basidiomycetes, 13 previously undescribed metabolites, (6 R,7 S,10 R)-7,10-epoxy-7,11-dimethyldodec-1-ene-6,11-diol (1) and 12 sesquiterpenes named elgonenes A-L (2-13), and the known compound P-coumaric acid (14) were isolated from a basidiomycete collected in Mount Elgon Natural Reserve. The producing organism represents a new species of the genus Sanghuangporus, which is one of the segregates of the important traditional Asian medicinal mushrooms that were formerly known as the " Inonotus linteus" complex. The structure elucidation of compounds 1-13, based on 2D NMR spectroscopy, high-resolution mass spectrometry, and other spectral methods, and their antibacterial, antifungal, and cytotoxic activities are reported.
    • Seven New Cytotoxic and Antimicrobial Xanthoquinodins from Jugulospora vestita.

      Shao, Lulu; Marin-Felix, Yasmina; Surup, Frank; Stchigel, Alberto M; Stadler, Marc; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (MDPI, 2020-09-25)
      During the course of a screening for novel biologically active secondary metabolites produced by the Sordariomycetes (Ascomycota, Fungi), the ex-type strain of Jugulospora vestita was found to produce seven novel xanthone-anthraquinone heterodimers, xanthoquinodin A11 (1) and xanthoquinodins B10-15 (2-7), together with the already known compound xanthoquinodin B4 (8). The structures of the xanthoquinodins were determined by analysis of the nuclear magnetic resonance (NMR) spectroscopic and mass spectrometric data. Moreover, the absolute configurations of these metabolites were established by analysis of the 1H-1H coupling constants, nuclear Overhauser effect spectroscopy (NOESY) correlations, and Electronic Circular Dichroism (ECD) spectroscopic data. Antifungal and antibacterial activities as well as cytotoxicity of all compounds were tested. Xanthoquinodin B11 showed fungicidal activities against Mucor hiemalis [minimum inhibitory concentration (MIC) 2.1 µg/mL], Rhodotorula glutinis (MIC 2.1 µg/mL), and Pichia anomala (MIC 8.3 µg/mL). All the compounds 1-8 displayed anti-Gram-positive bacteria activity (MIC 0.2-8.3 µg/mL). In addition, all these eight compounds showed cytotoxicity against KB 3.1, L929, A549, SK-OV-3, PC-3, A431, and MCF-7 mammalian cell lines. The six novel compounds (1-3, 5-7), together with xanthoquinodin B4, were also found in the screening of other strains belonging to Jugulospora rotula, revealing the potential chemotaxonomic significance of the compound class for the genus.
    • Silphiperfolene-Type Terpenoids and Other Metabolites from Cultures of the Tropical Ascomycete Hypoxylon rickii (Xylariaceae).

      Surup, Frank; Kuhnert, Eric; Liscinskij, Elena; Stadler, Marc; Helmholtz Centre for Infection Research, Inhoffenstraße 7, 38124 Braunschweig, Germany. (2015-06-16)
      A culture isolated from ascospores of Hypoxylon rickii, a xylariaceous ascomycete collected in Martinique, had yielded botryane, noreremophilane and abietane-type terpenoids in a preceding study, but additional metabolites were detected by extensive HPLC-MS analysis in other fractions. Herein we report the further isolation of four new sesquiterpenoids with a silphiperfol-6-ene skeleton from extracts of H. rickii. The planar structures were elucidated by NMR and HRMS data as 13-hydroxysilphiperfol-6-ene (1), 9-hydroxysilphiperfol-6-en-13-oic acid (2), 2-hydroxysilphiperfol-6-en-13-oic acid (3) and 15-hydroxysilphiperfol-6-en-13-oic acid (4). For compounds 2-4 we propose the trivial names rickinic acids A-C. Their stereochemistry was assigned by ROESY correlations as well as by the specific optical rotation. Additionally, the known compounds, botryenanol, dehydrobotrydienol, cyclo(Phe-Pro), cyclo(Pro-Leu), (+)-ramulosin and α-eleostearic acid were isolated. The antimicrobial and cytotoxic activities of the new compounds are also reported.
    • Simplicilones A and B Isolated from the Endophytic Fungus SPC3.

      Anoumedem, Elodie Gisèle M; Mountessou, Bel Youssouf G; Kouam, Simeon F; Narmani, Abolfazl; Surup, Frank; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (MDPI, 2020-10-29)
      Two new tetracyclic polyketides with a spirocenter, simplicilones A (1) and B (2) were isolated from the broth-culture of the endophytic fungus Simplicilliumsubtropicum (SPC3) in the course of our screening for new bioactive secondary metabolites. This endophytoic fungus is naturally harboured in the fresh bark of the Cameroonian medicinal plant Duguetia staudtii (Engl. and Diels) Chatrou. The planar structures of the simplicilones were elucidated by MS and 1D as well as 2D NMR spectroscopic techniques. The relative configuration was assigned by NOESY experiments in conjunction with coupling constants; subsequently, the absolute configurations were assigned by the modified Mosher's method. The compounds showed weak cytotoxic effects against the cell line KB3.1 (in vitro cytotoxicity (IC50) = 25 µg/mL for 1, 29 µg/mL for 2), but were inactive against the tested Gram-positive and Gram-negative bacteria as well as fungi.
    • Six Heterocyclic Metabolites from the Myxobacterium Labilithrix luteola.

      Mulwa, Lucky S; Jansen, Rolf; Praditya, Dimas F; Mohr, Kathrin I; Wink, Joachim; Steinmann, Eike; Stadler, Marc; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-02-28)
      Two new secondary metabolites, labindole A [2-methyl-3-(2-nitroethyl)-3H-indole] (1) and labindole B [2-methyl-3-(2-nitrovinyl)-3H-indole] (2), were isolated from the myxobacteriumLabilithrixluteola(DSM 27648T). Additionally, four metabolites3,4,5and6already known from other sources were obtained. Their structures were elucidated from high resolution electrospray ionisation mass spectrometry (HRESIMS) and 1D and 2D nuclear magnetic resonance (NMR) spectroscopy data and their relative configuration was assigned based on nuclear Overhauser effect (NOE) and vicinal ¹H-NMR coupling data. The compounds where tested for biological activities; labindoles A (1) and B (2) exhibited significant activity against Hepatitis C Virus, 9H-carbazole (3), 3-chloro-9H-carbazole (4) and 4-hydroxymethyl-quinoline (5) showed antifungal activities. Moreover, compound3had weak to moderate antibacterial activities, while labindoles A (1) and B (2) were devoid of significant antifungal and antibacterial effects.
    • Skeletocutins M-Q: biologically active compounds from the fruiting bodies of the basidiomycete Skeletocutis sp. collected in Africa.

      Cheng, Tian; Chepkirui, Clara; Decock, Cony; Matasyoh, Josphat C; Stadler, Marc; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Beilstein Institut, 2019-01-01)
      During the course of screening for new metabolites from basidiomycetes, we isolated and characterized five previously undescribed secondary metabolites, skeletocutins M-Q (1-5), along with the known metabolite tyromycin A (6) from the fruiting bodies of the polypore Skeletocutis sp. The new compounds did not exhibit any antimicrobial, cytotoxic, or nematicidal activities. However, compound 3 moderately inhibited the biofilm formation of Staphylococcus aureus (S. aureus), while compounds 3 and 4 performed moderately in the ʟ-leucine-7-amido-4-methylcoumarin (ʟ-Leu-AMC) inhibition assay. These compounds represent the first secondary metabolites reported to occur in the fruiting bodies by Skeletocutis. Interestingly, tyromycin A (6) was found to be the only common metabolite in fruiting bodies and mycelial cultures of the fungus, and none of the recently reported skeletocutins from the culture of the same strain were detected in the basidiomes.
    • Solubility and Stability Enhanced Oral Formulations for the Anti-Infective Corallopyronin A.

      Krome, Anna K; Becker, Tim; Kehraus, Stefan; Schiefer, Andrea; Steinebach, Christian; Aden, Tilman; Frohberger, Stefan J; López Mármol, Álvaro; Kapote, Dnyaneshwar; Jansen, Rolf; et al. (MDPI, 2020-11-18)
      Novel-antibiotics are urgently needed to combat an increase in morbidity and mortality due to resistant bacteria. The preclinical candidate corallopyronin A (CorA) is a potent antibiotic against Gram-positive and some Gram-negative pathogens for which a solid oral formulation was needed for further preclinical testing of the active pharmaceutical ingredient (API). The neat API CorA is poorly water-soluble and instable at room temperature, both crucial characteristics to be addressed and overcome for use as an oral antibiotic. Therefore, amorphous solid dispersion (ASD) was chosen as formulation principle. The formulations were prepared by spray-drying, comprising the water-soluble polymers povidone and copovidone. Stability (high-performance liquid chromatography, Fourier-transform-infrared spectroscopy, differential scanning calorimetry), dissolution (biphasic dissolution), and solubility (biphasic dissolution, Pion's T3 apparatus) properties were analyzed. Pharmacokinetic evaluations after intravenous and oral administration were conducted in BALB/c mice. The results demonstrated that the ASD formulation principle is a suitable stability- and solubility-enhancing oral formulation strategy for the API CorA to be used in preclinical and clinical trials and as a potential market product.
    • Sparticolins A-G, Biologically Active Oxidized Spirodioxynaphthalene Derivatives from the Ascomycete Sparticola junci.

      Phukhamsakda, Chayanard; Macabeo, Allan Patrick G; Huch, Volker; Cheng, Tian; Hyde, Kevin D; Stadler, Marc; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (American Society of Chemistry, 2019-10-25)
      To explore the chemical diversity of metabolites from new species of Dothideomycetes, the ex-type strain of Sparticola junci was investigated. Seven highly oxygenated and functionalized spirodioxynaphthalene natural products incorporating carboxyalkylidene-cyclopentanoid (1-4), carboxyl-functionalized oxabicyclo[3.3.0]octane (5-6), and annelated 2-cyclopentenone/δ-lactone (7) units, sparticolins A-G, were isolated from submerged cultures of the fungus. Their chemical structures including their relative (and absolute) configurations were established through spectroscopic and X-ray crystallographic analyses. Sparticolin B (2) exhibited inhibitory activity against the Gram-positive bacteria Bacillus subtilis, Micrococcus luteus, and Staphylococcus aureus, while sparticolin G (7) showed antifungal activities against Schizosaccharomyces pombe and Mucor hiemalis. All other sparticolins were only weakly active against S. aureus and also showed weak activities against the nematode Caenorhabditis elegans. Compounds 2 and 7 also showed moderate cytotoxic activities against seven mammalian cell lines.
    • Special issue: The contributions of Erio Camporesi

      Phukhamsakda, Chayanard; Wijayawardene, Nalin N.; Ariyawansa, Hiran A.; Senanayake, Indunil C.; Li, Wen-Jing; Wanasinghe, Dhanushka N.; Phookamsak, Rungtiwa; Tian, Qing; Daranagama, Dinushani A.; Thambugala, Kasun M.; et al. (Springer Science and Business Media LLC, 2020-03-23)
      [No abstract available]
    • Stieleriacines, N-Acyl Dehydrotyrosines From the Marine Planctomycete Stieleria neptunia sp. nov.

      Sandargo, Birthe; Jeske, Olga; Boedeker, Christian; Wiegand, Sandra; Wennrich, Jan-Peer; Kallscheuer, Nicolai; Jogler, Mareike; Rohde, Manfred; Jogler, Christian; Surup, Frank; et al. (Frontiers, 2020-07-16)
      Bacteria of the phylum Planctomycetes occur ubiquitously in marine environments and play important roles in the marine nitrogen- and carbon cycle, for example as scavengers after phototrophic blooms. Here, we describe the isolation and characterization of the planctomycetal strain Enr13T isolated from a Posidonia sp. biofilm obtained from seawater sediment close to Panarea Island, Italy. Phylogenetic tree reconstruction based on 16S rRNA gene sequences and multi-locus sequence analysis supports the delineation of strain Enr13T from characterized species part of the phylum of Planctomycetes. HPLC-MS analysis of culture broth obtained from strain Enr13T revealed the presence of lipophilic metabolites, of which the major compound was isolated by preparative reversed-phase HPLC. The structure of this compound, named stieleriacine D (1), was elucidated utilizing HRESIMS, 1D- and 2D-NMR data as a new N-acylated dehydrotyrosine derivative. Its biosynthesis was proposed based on an in silico gene cluster analysis. Through analysis of the MS/MS spectrum of 1 and its minor derivative, stieleriacine E (2), it was possible to assign the structure of 2 without isolation. 1 showed antibacterial activity, however, the wide distribution of structurally related compounds indicates a potential role as a signaling molecule.
    • Structurally diverse metabolites from the rare actinobacterium Saccharothrix xinjiangensis.

      Babadi, Zahra Khosravi; Sudarman, Enge; Ebrahimipour, Gholam Hossein; Primahana, Gian; Stadler, Marc; Wink, Joachim; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Japan Antibiotics Research Association, 2019-08-26)
      The bioassay-guided fractionation from cultures of the actinobacterium Saccharothrix xinjiangensis Act24Zk, collected from the Caspian Sea beach in Iran led to the isolation of three new compounds, caerulomycin M (1), saccharopyrone (2), and saccharonoic acid (3), together with the known compound, caerulomycin A (4). Their structures were elucidated from HR-ESIMS and 1D and 2D NMR data. Compound 2 displayed moderate cytotoxic activity against the human cervix carcinoma HeLa cells KB3.1 with an IC50 value of 5.4 µM.
    • Structures of an RNA polymerase promoter melting intermediate elucidate DNA unwinding.

      Boyaci, Hande; Chen, James; Jansen, Rolf; Darst, Seth A; Campbell, Elizabeth A; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Nature publishing group, 2019-01-09)
      A key regulated step of transcription is promoter melting by RNA polymerase (RNAP) to form the open promoter complex
    • Studies on the biologically active secondary metabolites of the new spider parasitic fungus Gibellula gamsii

      Kuephadungphan, Wilawan; Macabeo, Allan Patrick G.; Luangsa-Ard, Janet Jennifer; Tasanathai, Kanoksri; Thanakitpipattana, Donnaya; Phongpaichit, Souwalak; Yuyama, Kamila; Stadler, Marc
    • Study of three interesting Amanita species from Thailand: Morphology, multiple-gene phylogeny and toxin analysis.

      Thongbai, Benjarong; Miller, Steven L; Stadler, Marc; Wittstein, Kathrin; Hyde, Kevin D; Lumyong, Saisamorn; Raspé, Olivier; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017)
      Amanita ballerina and A. brunneitoxicaria spp. nov. are introduced from Thailand. Amanita fuligineoides is also reported for the first time from Thailand, increasing the known distribution of this taxon. Together, those findings support our view that many taxa are yet to be discovered in the region. While both morphological characters and a multiple-gene phylogeny clearly place A. brunneitoxicaria and A. fuligineoides in sect. Phalloideae (Fr.) Quél., the placement of A. ballerina is problematic. On the one hand, the morphology of A. ballerina shows clear affinities with stirps Limbatula of sect. Lepidella. On the other hand, in a multiple-gene phylogeny including taxa of all sections in subg. Lepidella, A. ballerina and two other species, including A. zangii, form a well-supported clade sister to the Phalloideae sensu Bas 1969, which include the lethal "death caps" and "destroying angels". Together, the A. ballerina-A. zangii clade and the Phalloideae sensu Bas 1969 also form a well-supported clade. We therefore screened for two of the most notorious toxins by HPLC-MS analysis of methanolic extracts from the basidiomata. Interestingly, neither α-amanitin nor phalloidin was found in A. ballerina, whereas Amanita fuligineoides was confirmed to contain both α-amanitin and phalloidin, and A. brunneitoxicaria contained only α-amanitin. Together with unique morphological characteristics, the position in the phylogeny indicates that A. ballerina is either an important link in the evolution of the deadly Amanita sect. Phalloideae species, or a member of a new section also including A. zangii.
    • Successful cultivation of a valuable wild strain of Lepista sordida from Thailand

      Thongbai, Benjarong; Wittstein, Kathrin; Richter, Christian; Miller, Steven L.; Hyde, Kevin D.; Thongklang, Naritsada; Klomklung, Namphung; Chukeatirote, Ekachai; Stadler, Marc; Helmholtz Centre for infection researchGmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-01-06)
    • Synthesis and Bioactivity of a Macrocidin B Stereoisomer.

      Weber, Stefanie E; Gaß, Juliane; Zeng, Haoxuan; Erb-Brinkmann, Maike; Schobert, Rainer; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (ACS, 2021-10-11)
      A stereoisomer of macrocidin B, a presumed metabolite of the fungus Phoma macrostoma, was synthesized in 18 steps and 2.7% yield from protected l-tyrosine that was N-β-ketoacylated with a fully functionalized octanoyl Meldrum's acid. Dieckmann condensation gave a 3-acyltetramic acid, which was macrocyclized via Williamson etherification between the phenol and epi-bromohydrin termini. This macrocidin B stereoisomer showed a weaker herbicidal effect than macrocidin A and no similar inhibitory effect on biofilms of Staphylococcus aureus.
    • Synthesis and Bioactivity of Ancorinoside B, a Marine Diglycosyl Tetramic Acid

      Soliga, Kevin J; Bär, Sofia I; Oberhuber, Natalie; Zeng, Haoxuan; Schrey, Hedda; Schobert, Rainer; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (MDPI, 2021-10-19)
      The sponge metabolite ancorinoside B was prepared for the first time in 16 steps and 4% yield. It features a β-d-galactopyranosyl-(1→4)-β-d-glucuronic acid tethered to a d-aspartic acid-derived tetramic acid. Key steps were the synthesis of a fully protected d-lactose derived thioglycoside, its attachment to a C20-aldehyde spacer, functionalization of the latter with a terminal N-(β-ketoacyl)-d-aspartate, and a basic Dieckmann cyclization to close the pyrrolidin-2,4-dione ring with concomitant global deprotection. Ancorinoside B exhibited multiple biological effects of medicinal interest. It inhibited the secretion of the cancer metastasis-relevant matrix metalloproteinases MMP-2 and MMP-9, and also the growth of Staphylococcus aureus biofilms by ca 87% when applied at concentrations as low as 0.5 µg/mL. This concentration is far below its MIC of ca 67 µg/mL and thus unlikely to induce bacterial resistance. It also led to a 67% dispersion of preformed S. aureus biofilms when applied at a concentration of ca 2 µg/mL. Ancorinoside B might thus be an interesting candidate for the control of the general hospital, catheter, or joint protheses infections.