Halogenated arenes are important building blocks in medicinal and agrochemistry. Chemical electrophilic aromatic halogenation requires molecular halogen, whereas FAD-dependent halogenases form halogenated with high regioselectivity while only halide salts O2 required. This reaction proceeds at room temperature aqueous media. However, enzymatic is considered inefficient, mainly because not stable. Thus, the preparative application remained elusive. We were able to show that long-term...

Flavin-dependent halogenases catalyse halogenation of aromatic compounds. In most cases, this reaction proceeds with high regioselectivity and requires only the presence FADH2, oxygen, halide salts. Since marine habitats contain concentrations halides, organisms populating oceans might be valuable sources yet undiscovered halogenases. A new Hidden-Markov-Model (HMM) based on PFAM tryptophan halogenase model was used for analysis metagenomes. Eleven metagenomes were screened leading to...

Abstract Regioselective methods to establish carbon–halide bonds are still rare, although halogenation is considered as a commonly used methodology for the functionalization of organic compounds. The incorporation halogen substituents by synthesis usually requires hazardous conditions, shows poor regioselectivity and results in formation unwanted byproducts. In addition, electrophilic aromatic substitution (S E Ar) obeys distinct rules depending on electron‐withdrawing or ‐donating groups...

Abstract Biocatalytic halogenation with tryptophan halogenases is hampered by severe limitations such as low activity and stability. These drawbacks can be overcome directed evolution, but for screening large mutant libraries, a facile high‐throughput method required. Therefore, we developed quantitative halogenase assay based on Suzuki–Miyaura cross‐coupling towards the formation of fluorescent aryltryptophan. The technique was optimized application in crude E. coli lysate without...

Abstract The combination of the biocatalytic halogenation l ‐tryptophan with subsequent chemocatalytic Suzuki–Miyaura cross‐coupling reactions leads to modular synthesis an array C5, C6, or C7 aryl‐substituted tryptophan derivatives. In a three‐step one‐pot reaction, bromo substituent is initially incorporated regioselectively by immobilized 5‐, 6‐, 7‐halogenases, respectively, concomitant cofactor regeneration. proceeds in aqueous media at room temperature presence NaBr and O 2 . After...

Flavin-dependent halogenases increasingly attract attention as biocatalysts in organic synthesis, facilitating environmentally friendly halogenation strategies that require only FADH2, oxygen, and halide salts. Different flavin-dependent tryptophan regioselectively chlorinate or brominate trypto-phan's indole moiety at C5, C6, C7. Here, we present the first substrate-bound structure of a 6-halogenase, namely Thal, also known ThdH, from bacterium Streptomyces albogriseolus 2.55 Å resolution....

The crystal structure and unambiguous absolute configuration of meleagrin (1) isolated from fungus Emericella dentata Nq45 is reported herein to first time on the bases single X-ray diffraction. Together with 1, haenamindole (2), isorugulosuvine (3), secalonic acid D (4), ergosterol (5) cerebroside A (6) were obtained their structures determined by ESI MS NMR data analysis. Diverse biological activity was investigated. Compound 1 pronounced potent cytotoxicity against human cervix carcinoma...

Flavin-dependent halogenases are known to regioselectively introduce halide substituents into aromatic moieties, for example, the indole ring of tryptophan. The process requires salts and oxygen instead molecular halogen in chemical halogenation. However, reduced cofactor flavin adenine dinucleotide (FADH2) has be regenerated using a reductase. Consequently, coupled biocatalytic steps usually applied regeneration. Nicotinamide (NADH) mimics can employed stoichiometrically replace enzymatic...

Abstract Flavin‐dependent tryptophan halogenases provide a regioselective access to chlorinated and brominated indole derivatives under mild conditions. Application of the halogenase requires regeneration system for reduced flavin cofactor FADH 2 , which is usually achieved by enzymatic or chemical reactions. We employed PyrH from Streptomyces rugosporus as model establish photochemical approach using blue light reductant . In contrast previous light‐driven biocatalysis flavin, conversion...

Abstract Halogenierte Arene stellen wichtige Bausteine in Medizinalchemie und Agrochemie dar. Chemische elektrophile aromatische Halogenierungen verwenden elementare Halogene, während FAD‐abhängige Halogenasen lediglich Halogenidsalze O 2 bei Raumtemperatur wässrigem Milieu für die regioselektive Halogenierung benötigen. Enzymatische galten als ineffizient aufgrund der mangelnden Stabilität Halogenasen, was präparative Anwendung limitierte. Wir konnten zeigen, dass Langzeitstabilität damit...

Four new para-benzoquinone containing abietane-type diterpenoids (1-4) along with thirteen known (5-17) were isolated from the roots of Plectranthus punctatus. The structures compounds established by detailed spectroscopic analyses and comparison literature data. tested for their antibacterial cytotoxic activity showed significant inhibitory against all bacterial strains used, 6, 8, 10, 11 showing an inhibition zone Staphylococcus warneri even greater than reference drug, gentamycin.

Terretonin N (1), a new highly oxygenated and unique tetracyclic 6-hydroxymeroterpenoid, was isolated together with seven known compounds from the ethyl acetate extract of solid-state fermented culture Nocardiopsis sp. Their structures were elucidated by spectroscopic analysis. The structure absolute configuration 1 unambiguously determined X-ray crystallography. isolation taxonomic characterization is reported. antimicrobial activity cytotoxicity strain compound studied using different...

Cryptophycins are potent tubulin polymerization inhibitors with picomolar antiproliferative potency in vitro and activity against multidrug-resistant (MDR) cancer cells. Because of neurotoxic side effects limited efficacy vivo, cryptophycin-52 failed as a clinical candidate treatment. However, this class compounds has emerged attractive payloads for tumor-targeting applications. In study, cryptophycin was conjugated to the cyclopeptide

A study of diterpenoids as active ingredients against cancer from the roots extract Casearia barteri Mast. (IC50 = 1.57 μg mL-1) led to isolation six new clerodane diterpenoids, named barterins A-F (1-6) alongside seven known compounds, caseamembrin A, E, casearlucin graveospene G, N-trans-feruloyltyramine, N-cis-feruloytyramine and sitosterol-3-O-β-D-(6-O-palmitoyl)-glucopyranoside. Their structures were elucidated based on NMR spectroscopic data mass spectrometry. The absolute...

Abstract Flavin‐dependent halogenases selectively introduce halogen substituents into (hetero‐)aromatic substrates and require only molecular oxygen halide salts for this regioselective oxidative CH‐functionalization. Genomic analysis of Xanthomonas campestris pv. B100 identified three novel putative members enzyme class. They were shown to into, e. g., substituted indoles, while preferring bromide over chloride. magnified image

Isoshamixanthone (1), a new stereoisomeric pyrano xanthone together with the previously known fungal metabolites, epiisoshamixanthone (2), sterigmatocystin (3), arugosin C (4), norlichexanthone (5), diorcinol (6), ergosterol and methyllinoleate, were obtained from endophytic strain Aspergillus sp. ASCLA isolated leaf tissues of medicinal plant Callistemon subulatus. The chemical structure (1) was elucidated by extensive 1D, 2D NMR, ESI HR mass measurements, comparison literature data....

Phytochemical investigation of the ethyl acetate extract roots Aloe megalacantha led to isolation four new natural products—1,8-dimethoxynepodinol (1), aloesaponarin III (2), 10-O-methylchrysalodin (3) and methyl-26-O-feruloyl-oxyhexacosanate (4)—along with ten known compounds. All purified metabolites were characterized by NMR, mass spectrometric analyses comparison literature data. The isolates evaluated for their cytotoxic activity against a human cervix carcinoma cell line KB-3-1 some...

Terretonin O (1), a new meroterpenoid, was isolated individually from both methanolic extracts of thermophilic Aspergillus terreus TM8 and marine LGO13. The recently reported terretonins M (2) N (3) were further the fungus LGO13 along with nine known compounds, terrelumamide A (4), terrein (5), methyl-3,4,5-trimethoxyl-2-[2-(nicotinamide)benzamido] benzoate (6), butyrolactones I-III (7–9), aspulvinone (10), ergosterol, ergost-4-ene-3-one methyl linoleate. Structure terretonin (1) established...

Abstract Die Anwendung von Tryptophan‐Halogenasen für die enzymatische Halogenierung hat noch gravierende Limitierungen. Diese könnten mittels gerichteter Evolution überwunden werden, jedoch bedarf Durchmusterung großer Mutantenbibliotheken eines robusten Hochdurchsatz‐fähigen Testsystems. Im Hinblick darauf wurde eine Suzuki‐Miyaura‐Kreuzkupplung als quantitativer Halogenase‐Assay auf Basis der Bildung fluoreszierenden Aryltryptophans entwickelt. Methode im E.‐coli‐Lysat ohne intermediäre...

Tumor targeting has emerged as an advantageous approach to improving the efficacy and safety of cytotoxic agents or radiolabeled ligands that do not preferentially accumulate in tumor tissue. The somatostatin receptors (SSTRs) belong G-protein-coupled receptor superfamily they are overexpressed many neuroendocrine tumors (NETs). SSTRs can be efficiently targeted with octreotide, a cyclic octapeptide is derived from native somatostatin. conjugation cargoes octreotide represents attractive for...