"Novel chemo-enzymatic synthesis, structural elucidation and first antiprotozoal activity profiling of the atropoisomeric dimers of trans-8-Hydroxycalamenene".

Leishmaniasis and malaria are two debilitating protozoan diseases affecting millions globally, particularly in tropical and subtropical regions. Current therapeutic options face significant challenges due to emerging drug-resistant strains, necessitating the discovery of novel antiprotozoal agents. This study explores, for the first time, the antiprotozoal potential of calamenenes and their dimers, naturally occurring sesquiterpenes found in essential oils, through a novel chemo-enzymatic synthesis approach.

Studies on the Oxidation of Aromatic Amines Catalyzed by Laccase.

The bio-oxidation of a series of aromatic amines catalyzed by laccase has been investigated exploiting either commercially available nitrogenous substrates [()-4-vinyl aniline and diphenyl amine] or ad hoc synthetized ones [()-4-styrylaniline, ()-4-(prop-1-en-1-yl)aniline and ()-4-(((4-methoxyphenyl)imino)methyl)phenol]. At variance to their phenolic equivalents, the investigated aromatic amines were not converted into the expected cyclic dimeric structures under catalysis. The formation of complex oligomeric/polymeric or decomposition by-products was mainly observed, with the exception of the isolation of two interesting but unexpected chemical skeletons.

Functional Characterization and Synthetic Application of Is2-SDR, a Novel Thermostable and Promiscuous Ketoreductase from a Hot Spring Metagenome.

In a metagenome mining-based search of novel thermostable hydroxysteroid dehydrogenases (HSDHs), enzymes that are able to selectively oxidize/reduce steroidal compounds, a novel short-chain dehydrogenase/reductase (SDR), named Is2-SDR, was recently discovered. This enzyme, found in an Icelandic hot spring metagenome, shared a high sequence similarity with HSDHs, but, unexpectedly, showed no activity in the oxidation of the tested steroid substrates, e.g.

Stereoselective Biocatalyzed Reductions of Ginger Active Components Recovered from Industrial Wastes.

Ginger is among the most widespread and widely consumed traditional medicinal plants around the world. Its beneficial effects, which comprise e. g.

Discovery and Characterization of a Novel Thermostable β-Amino Acid Transaminase from a Meiothermus Strain Isolated in an Icelandic Hot Spring.

A Meiothermus strain capable of using β-phenylalanine for growth is isolated by culture enrichment of samples collected in hot environments and the genome is sequenced showing the presence of 22 putative transaminase (TA) sequences. On the basis of phylogenetic and sequence analysis, a TA termed Ms-TA2 is selected for further studies. The enzyme is successfully produced in Escherichia coli Rosetta(DE3) cells, with 70 mg of pure protein obtained from 1 L culture after purification by affinity chromatography.

Studies on the Catalytic Promiscuity of Limonene Epoxide Hydrolases in the Non-hydrolytic Ring Opening of 1,2-Epoxides.

The non-hydrolytic ring opening of 1,2-epoxides in the presence of limonene epoxide hydrolases (LEHs) and different nucleophiles has been investigated. Lyophilized, wild-type LEHs were tested in selected water-saturated organic solvents in the presence of cyclohexene oxide as substrate and different alcohols, thiols and primary amines as nucleophiles. Although the LEHs retained an appreciable catalytic activity under different reaction conditions, formation of the desired 1,2-substituted cyclohexanols was not observed.

Stereoselectivity Switch in the Reduction of α-Alkyl-β-Arylenones by Structure-Guided Designed Variants of the Ene Reductase OYE1.

Ene reductases from the Old Yellow Enzyme (OYE) family are industrially interesting enzymes for the biocatalytic asymmetric reduction of alkenes. To access both enantiomers of the target reduced products, stereocomplementary pairs of OYE enzymes are necessary, but their natural occurrence is quite limited. A library of wild type ene reductases from different sources was screened in the stereoselective reduction of a set of representative α-alkyl-β-arylenones to investigate the naturally available biodiversity.

Self-assembling Releasable Thiocolchicine-Diphenylbutenylaniline Conjugates.

The design and the synthesis of new self-assembling conjugates is reported. The target compounds are characterized by the presence of a self-immolative linker that secures a controlled release induced by lipase cleavage. 4-(1,2-Diphenylbut-1-en-1-yl)aniline is used as a self-assembling inducer and amino-thiocolchicine as prototype of drug.

Chemo-enzymatic synthesis of (E)-2,3-diaryl-5-styryl-trans-2,3-dihydrobenzofuran-based scaffolds and their in vitro and in silico evaluation as a novel sub-family of potential allosteric modulators of the 90 kDa heat shock protein (Hsp90).

Herein we propose a facile, versatile and selective chemo-enzymatic synthesis of substituted (E)-2,3-diaryl-5-styryl-trans-2,3-dihydrobenzofurans based on the exploitation of the laccase-mediated oxidative (homo)coupling of (E)-4-styrylphenols. Thanks to this novel synthetic strategy, a library of benzofuran-based potential allosteric activators of the Heat shock protein 90 (Hsp90) was easily prepared. Moreover, considering their structural analogies to previously reported allosteric modulators, the sixteen new compounds synthesized in this work were tested in vitro for their potential stimulatory action on the ATPase activity of the molecular chaperone Hsp90.

Novel thermostable amine transferases from hot spring metagenomes.

Hot spring metagenomes, prepared from samples collected at temperatures ranging from 55 to 95 °C, were submitted to an in silico screening aimed at the identification of novel amine transaminases (ATAs), valuable biocatalysts for the preparation of optically pure amines. Three novel (S)-selective ATAs, namely Is3-TA, It6-TA, and B3-TA, were discovered in the metagenome of samples collected from hot springs in Iceland and in Italy, cloned from the corresponding metagenomic DNAs and overexpressed in recombinant form in E. coli.

A Sustainable One-Pot, Two-Enzyme Synthesis of Naturally Occurring Arylalkyl Glucosides.

A sustainable, convenient, scalable, one-pot, two-enzyme method for the glucosylation of arylalkyl alcohols was developed. The reaction scheme is based on a transrutinosylation catalyzed by a rutinosidase from A. niger using the cheap commercially available natural flavonoid rutin as glycosyl donor, followed by selective "trimming" of the rutinoside unit catalyzed by a rhamnosidase from A.

Correction: Self-assembled 4-(1,2-diphenylbut-1-en-1-yl)aniline based nanoparticles: podophyllotoxin and aloin as building blocks.

Correction for 'Self-assembled 4-(1,2-diphenylbut-1-en-1-yl)aniline based nanoparticles: podophyllotoxin and aloin as building blocks' by Gaia Fumagalli, et al., Org. Biomol.

Self-assembled 4-(1,2-diphenylbut-1-en-1-yl)aniline based nanoparticles: podophyllotoxin and aloin as building blocks.

The ability of 4-(1,2-diphenylbut-1-en-1-yl)aniline as a self-assembly inducer is reported. The conjugation of this moiety with aloin or podophyllotoxin resulted in spherical nanoparticles that were characterized by Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM) and NanoSight technology. A preliminary biological evaluation on two cancer cell lines is reported.

Novel flavonolignan hybrid antioxidants: From enzymatic preparation to molecular rationalization.

A series of antioxidants was designed and synthesized based on conjugation of the hepatoprotective flavonolignan silybin with l-ascorbic acid, trolox alcohol or tyrosol via a C aliphatic linker. These hybrid molecules were prepared from 12-vinyl dodecanedioate-23-O-silybin using the enzymatic regioselective acylation procedure with Novozym 435 (lipase B) or with lipase PS. Voltammetric analyses showed that the silybin-ascorbic acid conjugate exhibited excellent electron donating ability, in comparison to the other conjugates.

Structural and biochemical insights into 7β-hydroxysteroid dehydrogenase stereoselectivity.

Hydroxysteroid dehydrogenases are of great interest as biocatalysts for transformations involving steroid substrates. They feature a high degree of stereo- and regio-selectivity, acting on a defined atom with a specific configuration of the steroid nucleus. The crystal structure of 7β-hydroxysteroid dehydrogenase from Collinsella aerofaciens reveals a loop gating active-site accessibility, the bases of the specificity for NADP(+) , and the general architecture of the steroid binding site.

Insights into the properties of the two enantiomers of trans-δ-viniferin, a resveratrol derivative: antioxidant activity, biochemical and molecular modeling studies of its interactions with hemoglobin.

Resveratrol is widely known as an antioxidant and anti-inflammatory molecule. The present study first reports the effects of trans-δ-viniferin (TVN), a dimer of resveratrol, on human erythrocytes. The antioxidant activity of TVN was tested using in vitro model systems such as hydroxy radical scavenging, DPPH and lipid peroxidation.

Dicarboxylic esters: Useful tools for the biocatalyzed synthesis of hybrid compounds and polymers.

Dicarboxylic acids and their derivatives (esters and anhydrides) have been used as acylating agents in lipase-catalyzed reactions in organic solvents. The synthetic outcomes have been dimeric or hybrid derivatives of bioactive natural compounds as well as functionalized polyesters.

Regioselective alcoholysis of silychristin acetates catalyzed by lipases.

A panel of lipases was screened for the selective acetylation and alcoholysis of silychristin and silychristin peracetate, respectively. Acetylation at primary alcoholic group (C-22) of silychristin was accomplished by lipase PS (Pseudomonas cepacia) immobilized on diatomite using vinyl acetate as an acetyl donor, whereas selective deacetylation of 22-O-acetyl silychristin was accomplished by Novozym 435 in methyl tert-butyl ether/ n-butanol. Both of these reactions occurred without diastereomeric discrimination of silychristin A and B.

Hemp hurds biorefining: A path to green L-(+)-lactic acid production.

Sugars streams generated by organosolv pretreatment of hemp hurds, cellulose (C6) and hemicellulose (C5) fractions, were fermented to lactic acid (LA) by Bacillus coagulans strains XZL4 and DSM1. Pretreatment conditions and enzymatic hydrolysis were optimized and B. coagulans aptness to use lignocellulosic-derived sugars as a carbon source was evaluated.

Fractionation of hemp hurds by organosolv pretreatment and its effect on production of lignin and sugars.

Fractionation of hemp hurds into its three main components, cellulose, hemicellulose, and lignin, was carried out using organosolv pretreatment. The effect of processing parameters, such as temperature, catalyst concentration, reaction time, and methanol (MeOH) concentration, on the dissolution and recovery of hemicellulose and lignin was determined. More than 75% of total hemicellulose and 75% of total lignin was removed in a single step with low amounts of degradation products under the following conditions: 165 °C, 3% H2 SO4 , 20 min reaction time, and 45% MeOH.

The quest for new mild and selective modifications of natural structures: laccase-catalysed oxidation of ergot alkaloids leads to unexpected stereoselective C-4 hydroxylation.

Laccase-catalysed oxidation of ergot alkaloids in the absence of chemical mediators allowed the unexpected isolation of the mono-hydroxylated derivatives of compounds 2-7. Structure determination by NMR techniques clearly indicated that hydroxylation took place at the C-4 benzylic position. Quite notably, the proposed protocol allowed, for the first time, functionalisation at the C-4 position of the ergoline skeleton.

In search of sustainable chemical processes: cloning, recombinant expression, and functional characterization of the 7α- and 7β-hydroxysteroid dehydrogenases from Clostridium absonum.

Nicotinamide adenine dinucleotide phosphate-dependent 7α-hydroxysteroid dehydrogenase (7α-HSDH) and 7β-hydroxysteroid dehydrogenases (7β-HSDH) from Clostridium absonum catalyze the epimerization of primary bile acids through 7-keto bile acid intermediates and may be suitable as biocatalysts for the synthesis of bile acids derivatives of pharmacological interest. C. absonum 7α-HSDH has been purified to homogeneity and the N-terminal sequence has been determined by Edman sequencing.