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Novel Drugs by Biotransformation—in Memory of the Late Scientists Frieder...
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Novel Drugs by Biotransformation—in Memory of the Late Scientists Frieder Schauer and Peter Grunwald

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Microbial Biotechnology".

Deadline for manuscript submissions: closed (30 December 2022) | Viewed by 13383

Special Issue Editors

Dr. Annett Mikolasch

E-Mail Website
Guest Editor
Institute for Microbiology, University of Greifswald, Greifswald, Germany
Interests: biotransformation; drugs; antibiotics; laccase
Special Issues, Collections and Topics in MDPI journals
Dr. Mariam Gaid

E-Mail Website
Guest Editor
Technische Universität Braunschweig, 38106 Braunschweig, Germany
Interests: plant secondary metabolism; biosynthesis and biotechnology of polyprenylated aromatic polyketides; transgenesis; plant tissue culture; biosynthesis of benzoic acid-based phytoalexins such as xanthones and biphenyls
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Isolated enzymes or whole microbial cells are environmentally friendly catalysts which can be used in aqueous solution at room temperature, atmospheric pressure, and moderate pH values and are therefore well suited for the green synthesis of novel drugs. Microbial enzymes transform numerous substances in a reaction-, region-, and stereospecific way and thus in many cases may meet the requirements of modern drug synthesis. Of particular practical value is the fact that they not only catalyze the reactions of their natural substrates but also convert other compounds. Biotechnological processes use whole cells and/or specific enzymes. Biosynthetic processes, which often require a cascade of individual enzyme reactions, are usually carried out with whole cells, whereas biotransformation reactions use either isolated enzymes or whole cells depending on the properties of the enzymes involved. When evaluating a process, the advantages and disadvantages of isolated enzymes and whole cells must be weighed against each other, though where possible, specific enzymes tend to be preferred so as to exclude side reactions catalyzed by cells. This Special Issue will provide an insight into strategies of biosynthesis and biotransformation of novel drugs. The latest proven enzyme-mediated routes, using single-step biotransformation or enzyme cascade synthesis, will be discussed.

Dr. Annett Mikolasch
Dr. Mariam Gaid
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Microorganisms is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • biosynthesis
  • biotransformation
  • drugs
  • enzyme cascade synthesis
  • green synthesis
  • environmentally friendly catalyst

Published Papers (7 papers)

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Editorial

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2 pages, 173 KiB  
Editorial
Novel Drugs Obtained via Biotransformation—In Memory of the Late Scientists Frieder Schauer and Peter Grunwald
by Mariam Gaid and Annett Mikolasch
Microorganisms 2023, 11(7), 1734; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms11071734 - 01 Jul 2023
Viewed by 609
Abstract
The development of novel drugs is a complex process that requires cost-effective and sustainable techniques [...] Full article
(This article belongs to the Special Issue Novel Drugs by Biotransformation—in Memory of the Late Scientists Frieder Schauer and Peter Grunwald)

Research

Jump to: Editorial

25 pages, 1770 KiB  
Article
A Novel Antimicrobial Metabolite Produced by Paenibacillus apiarius Isolated from Brackish Water of Lake Balkhash in Kazakhstan
by Alexander Meene, Christiane Herzer, Rabea Schlüter, Bolatkhan Zayadan, Ruediger Pukall, Peter Schumann, Frieder Schauer, Tim Urich and Annett Mikolasch
Microorganisms 2022, 10(8), 1519; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10081519 - 27 Jul 2022
Cited by 2 | Viewed by 1626
Abstract
Four aerobic bacteria with bacteriolytic capabilities were isolated from the brackish water site Strait Uzynaral of Lake Balkhash in Kazakhstan. The morphology and physiology of the bacterial isolates have subsequently been analyzed. Using matrix assisted laser desorption ionization-time of flight mass spectrum and [...] Read more.
Four aerobic bacteria with bacteriolytic capabilities were isolated from the brackish water site Strait Uzynaral of Lake Balkhash in Kazakhstan. The morphology and physiology of the bacterial isolates have subsequently been analyzed. Using matrix assisted laser desorption ionization-time of flight mass spectrum and partial 16S rRNA gene sequence analyses, three of the isolates have been identified as Pseudomonas veronii and one as Paenibacillus apiarius. We determined the capability of both species to lyse pre-grown cells of the Gram-negative strains Pseudomonas putida SBUG 24 and Escherichia coli SBUG 13 as well as the Gram-positive strains Micrococcus luteus SBUG 16 and Arthrobacter citreus SBUG 321 on solid media. The bacteriolysis process was analyzed by creating growth curves and electron micrographs of co-cultures with the bacteriolytic isolates and the lysis sensitive strain Arthrobacter citreus SBUG 321 in nutrient-poor liquid media. One metabolite of Paenibacillus apiarius was isolated and structurally characterized by various chemical structure determination methods. It is a novel antibiotic substance. Full article
(This article belongs to the Special Issue Novel Drugs by Biotransformation—in Memory of the Late Scientists Frieder Schauer and Peter Grunwald)
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15 pages, 2918 KiB  
Article
Cutinase ACut2 from Blastobotrysraffinosifermentans for the Selective Desymmetrization of the Symmetric Diester Diethyl Adipate to the Monoester Monoethyl Adipate
by Marion Rauter, Daniela Nietz and Gotthard Kunze
Microorganisms 2022, 10(7), 1316; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10071316 - 29 Jun 2022
Cited by 1 | Viewed by 1257
Abstract
Monoethyl adipate (MEA) is a highly valuable monoester for activating resistance mechanisms and improving protective effects in pathogen-attacked plants. The cutinase ACut2 from the non-conventional yeast Blastobotrys (Arxula) raffinosifermentans (adeninivorans) was used for its synthesis by the desymmetrization of dicarboxylic acid diester diethyl [...] Read more.
Monoethyl adipate (MEA) is a highly valuable monoester for activating resistance mechanisms and improving protective effects in pathogen-attacked plants. The cutinase ACut2 from the non-conventional yeast Blastobotrys (Arxula) raffinosifermentans (adeninivorans) was used for its synthesis by the desymmetrization of dicarboxylic acid diester diethyl adipate (DEA). Up to 78% MEA with 19% diacid adipic acid (AA) as by-product could be synthesized by the unpurified ACut2 culture supernatant from the B. raffinosifermentans overexpression strain. By adjusting pH and enzyme concentration, the selectivity of the free ACut2 culture supernatant was increased, yielding 95% MEA with 5% AA. Selectivity of the carrier immobilized ACut2 culture supernatant was also improved by pH adjustment during immobilization, as well as carrier enzyme loading, ultimately yielding 93% MEA with an even lower AA concentration of 3–4%. Thus, optimizations enabled the selective hydrolysis of DEA into MEA with only a minor AA impurity. In the up-scaling, a maximum of 98% chemical and 87.8% isolated MEA yield were obtained by the adsorbed enzyme preparation with a space time yield of 2.6 g L−1 h−1. The high monoester yields establish the ACut2-catalyzed biosynthesis as an alternative to existing methods. Full article
(This article belongs to the Special Issue Novel Drugs by Biotransformation—in Memory of the Late Scientists Frieder Schauer and Peter Grunwald)
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18 pages, 6135 KiB  
Article
Novel Unspecific Peroxygenase from Truncatella angustata Catalyzes the Synthesis of Bioactive Lipid Mediators
by Rosalie König, Jan Kiebist, Johannes Kalmbach, Robert Herzog, Kai-Uwe Schmidtke, Harald Kellner, René Ullrich, Nico Jehmlich, Martin Hofrichter and Katrin Scheibner
Microorganisms 2022, 10(7), 1267; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10071267 - 22 Jun 2022
Cited by 3 | Viewed by 1951
Abstract
Lipid mediators, such as epoxidized or hydroxylated eicosanoids (EETs, HETEs) of arachidonic acid (AA), are important signaling molecules and play diverse roles at different physiological and pathophysiological levels. The EETs and HETEs formed by the cytochrome P450 enzymes are still not fully explored, [...] Read more.
Lipid mediators, such as epoxidized or hydroxylated eicosanoids (EETs, HETEs) of arachidonic acid (AA), are important signaling molecules and play diverse roles at different physiological and pathophysiological levels. The EETs and HETEs formed by the cytochrome P450 enzymes are still not fully explored, but show interesting anti-inflammatory properties, which make them attractive as potential therapeutic target or even as therapeutic agents. Conventional methods of chemical synthesis require several steps and complex separation techniques and lead only to low yields. Using the newly discovered unspecific peroxygenase TanUPO from the ascomycetous fungus Truncatella angustata, 90% regioselective conversion of AA to 14,15-EET could be achieved. Selective conversion of AA to 18-HETE, 19-HETE as well as to 11,12-EET and 14,15-EET was also demonstrated with known peroxygenases, i.e., AaeUPO, CraUPO, MroUPO, MweUPO and CglUPO. The metabolites were confirmed by HPLC-ELSD, MS1 and MS2 spectrometry as well as by comparing their analytical data with authentic standards. Protein structure simulations of TanUPO provided insights into its substrate access channel and give an explanation for the selective oxyfunctionalization of AA. The present study expands the scope of UPOs as they can now be used for selective syntheses of AA metabolites that serve as reference material for diagnostics, for structure-function elucidation as well as for therapeutic and pharmacological purposes. Full article
(This article belongs to the Special Issue Novel Drugs by Biotransformation—in Memory of the Late Scientists Frieder Schauer and Peter Grunwald)
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13 pages, 1020 KiB  
Article
Laccase-Catalyzed Derivatization of Aminoglycoside Antibiotics and Glucosamine
by Annett Mikolasch, Ulrike Lindequist, Sabine Witt and Veronika Hahn
Microorganisms 2022, 10(3), 626; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10030626 - 15 Mar 2022
Cited by 4 | Viewed by 1799
Abstract
The increasing demand for new and effective antibiotics requires intelligent strategies to obtain a wide range of potential candidates. Laccase-catalyzed reactions have been successfully applied to synthesize new β-lactam antibiotics and other antibiotics. In this work, laccases from three different origins were used [...] Read more.
The increasing demand for new and effective antibiotics requires intelligent strategies to obtain a wide range of potential candidates. Laccase-catalyzed reactions have been successfully applied to synthesize new β-lactam antibiotics and other antibiotics. In this work, laccases from three different origins were used to produce new aminoglycoside antibiotics. Kanamycin, tobramycin and gentamicin were coupled with the laccase substrate 2,5-dihydroxy-N-(2-hydroxyethyl)-benzamide. The products were isolated, structurally characterized and tested in vitro for antibacterial activity against various strains of Staphylococci, including multidrug-resistant strains. The cytotoxicity of these products was tested using FL cells. The coupling products showed comparable and, in some cases, better antibacterial activity than the parent antibiotics in the agar diffusion assay, and they were not cytotoxic. The products protected mice against infection with Staphylococcus aureus, which was lethal to the control animals. The results underline the great potential of laccases in obtaining new biologically active compounds, in this case new antibiotic candidates from the class of aminoglycosides. Full article
(This article belongs to the Special Issue Novel Drugs by Biotransformation—in Memory of the Late Scientists Frieder Schauer and Peter Grunwald)
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13 pages, 2959 KiB  
Article
Laccase-Catalyzed Derivatization of Antibiotics with Sulfonamide or Sulfone Structures
by Annett Mikolasch and Veronika Hahn
Microorganisms 2021, 9(11), 2199; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9112199 - 21 Oct 2021
Cited by 9 | Viewed by 1579
Abstract
Trametes spec. laccase (EC 1.10.3.2.) mediates the oxidative coupling of antibiotics with sulfonamide or sulfone structures with 2,5-dihydroxybenzene derivatives to form new heterodimers and heterotrimers. These heteromolecular hybrid products are formed by nuclear amination of the p-hydroquinones with the primary amino group [...] Read more.
Trametes spec. laccase (EC 1.10.3.2.) mediates the oxidative coupling of antibiotics with sulfonamide or sulfone structures with 2,5-dihydroxybenzene derivatives to form new heterodimers and heterotrimers. These heteromolecular hybrid products are formed by nuclear amination of the p-hydroquinones with the primary amino group of the sulfonamide or sulfone antibiotics, and they inhibited in vitro the growth of Staphylococcus species, including multidrug-resistant strains. Full article
(This article belongs to the Special Issue Novel Drugs by Biotransformation—in Memory of the Late Scientists Frieder Schauer and Peter Grunwald)
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27 pages, 4706 KiB  
Article
Genome and Secretome Analysis of Staphylotrichum longicolleum DSM105789 Cultured on Agro-Residual and Chitinous Biomass
by Arslan Ali, Bernhard Ellinger, Sophie C. Brandt, Christian Betzel, Martin Rühl, Carsten Wrenger, Hartmut Schlüter, Wilhelm Schäfer, Hévila Brognaro and Martin Gand
Microorganisms 2021, 9(8), 1581; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9081581 - 25 Jul 2021
Cited by 2 | Viewed by 2827
Abstract
Staphylotrichum longicolleum FW57 (DSM105789) is a prolific chitinolytic fungus isolated from wood, with a chitinase activity of 0.11 ± 0.01 U/mg. We selected this strain for genome sequencing and annotation, and compiled its growth characteristics on four different chitinous substrates as well as [...] Read more.
Staphylotrichum longicolleum FW57 (DSM105789) is a prolific chitinolytic fungus isolated from wood, with a chitinase activity of 0.11 ± 0.01 U/mg. We selected this strain for genome sequencing and annotation, and compiled its growth characteristics on four different chitinous substrates as well as two agro-industrial waste products. We found that the enzymatic mixture secreted by FW57 was not only able to digest pre-treated sugarcane bagasse, but also untreated sugarcane bagasse and maize leaves. The efficiency was comparable to a commercial enzymatic cocktail, highlighting the potential of the S. longicolleum enzyme mixture as an alternative pretreatment method. To further characterize the enzymes, which efficiently digested polymers such as cellulose, hemicellulose, pectin, starch, and lignin, we performed in-depth mass spectrometry-based secretome analysis using tryptic peptides from in-gel and in-solution digestions. Depending on the growth conditions, we were able to detect from 442 to 1092 proteins, which were annotated to identify from 134 to 224 putative carbohydrate-active enzymes (CAZymes) in five different families: glycoside hydrolases, auxiliary activities, carbohydrate esterases, polysaccharide lyases, glycosyl transferases, and proteins containing a carbohydrate-binding module, as well as combinations thereof. The FW57 enzyme mixture could be used to replace commercial enzyme cocktails for the digestion of agro-residual substrates. Full article
(This article belongs to the Special Issue Novel Drugs by Biotransformation—in Memory of the Late Scientists Frieder Schauer and Peter Grunwald)
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