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Biotransformation of Natural Products and Phytochemicals: Metabolites, Their Preparation and Properties

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 18453

Special Issue Editors

Laboratory of Biotransformation, Institute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, 14220 Prague, Czech Republic
Interests: polyphenols; flavonolignans; Silybum marianum; flavonols; quercetin; rutin; isoquercitrin; metabolites; gut microbiota; biotransformation by enzymes and whole cells
Special Issues, Collections and Topics in MDPI journals
Institute of Microbiology, Academy of Sciences of the Czech Republic, Laboratory of Biotransformation, National Centre of Biocatalysis and Biotransformation, Videnska 1083, CZ 142 20 Praha 4, Czech Republic
Interests: biocatalysis and biotransformation; immobilized microbial cells, their use in production and biotransformation of natural products; biotransformation of natural products by enzymes and microorganisms; preparation of glycosidases of microbial origin and their use for glycosylation of natural compounds: glycoconjugates, multivalent compounds, ergot alkaloids, flavonoids, antioxidants and chemoprotectants
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Biotransformation features two major meanings: (i) biocatalysis and enzymatic modification of various compounds and (ii) biotransformation in terms of metabolic changes of xenobiotics in organism. In this special issue we want to focus on both connotations of biotransformation; specifically to the biotransformation of natural products and phytochemicals. Metabolites of xenobiotics have often different biological and biophysical properties compared to the parent compounds. Besides inactivation, also toxication and/or alteration of their activities often happen. Phytochemicals and other natural products have received increased attention due to their considerable benefits in preventing and managing chronic diseases. These compounds generally suffer from low bioavailability, they are extensively metabolized and their metabolites are often responsible for their biological effects. Therefore preparation and detailed study of their metabolites is of utmost importance. Due to the complexity of phytochemicals enzymatic methods were recently introduced in the preparation of their (tentative) metabolites. Topics for this Special Issue include the discovery of new chemical and biochemical methods for metabolite preparation including multienzyme methods, advanced structural and analytical methods for their characterization, and determination of biological and biophysical properties of the metabolites.

Major requirements for papers submitted to this Special Issue are (i) clear novelty; (ii) reproducibility; (iii) molecular bases of reactions and processes; and (iv) defined chemical reactions and structures. Papers dealing with minor optimizations of known procedures, those using poorly defined substrates and products and poorly defined biocatalysts (enzymes) or organisms unavailable to other researchers will be returned without further review.

Dr. Kateřina Valentová
Prof. Dr. Vladimír Křen
Guest Editors

Manuscript Submission Information

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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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • natural product biotransformation
  • phytochemical metabolism
  • preparation of metabolites
  • cofactor regeneration
  • multienzyme processes
  • metabolite analysis and characterization
  • toxicology of the metabolites

Published Papers (8 papers)

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Editorial

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3 pages, 216 KiB  
Editorial
Biotransformation of Natural Products and Phytochemicals: Metabolites, Their Preparation, and Properties
by Kateřina Valentová
Int. J. Mol. Sci. 2023, 24(9), 8030; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24098030 - 28 Apr 2023
Cited by 2 | Viewed by 834
Abstract
The term “biotransformation” refers to the process by which various compounds are biocatalyzed and enzymatically modified, as well as the metabolic changes that occur in organisms as a result of exposure to xenobiotics [...] Full article

Research

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16 pages, 2839 KiB  
Article
Sulfation of Phenolic Acids: Chemoenzymatic vs. Chemical Synthesis
by Viola Kolaříková, Katerina Brodsky, Lucie Petrásková, Helena Pelantová, Josef Cvačka, Libor Havlíček, Vladimír Křen and Kateřina Valentová
Int. J. Mol. Sci. 2022, 23(23), 15171; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232315171 - 02 Dec 2022
Cited by 3 | Viewed by 1633
Abstract
Phenolic acids are known flavonoid metabolites, which typically undergo bioconjugation during phase II of biotransformation, forming sulfates, along with other conjugates. Sulfated derivatives of phenolic acids can be synthesized by two approaches: chemoenzymatically by 3′-phosphoadenosine-5′-phosphosulfate (PAPS)-dependent sulfotransferases or PAPS-independent aryl sulfotransferases such as [...] Read more.
Phenolic acids are known flavonoid metabolites, which typically undergo bioconjugation during phase II of biotransformation, forming sulfates, along with other conjugates. Sulfated derivatives of phenolic acids can be synthesized by two approaches: chemoenzymatically by 3′-phosphoadenosine-5′-phosphosulfate (PAPS)-dependent sulfotransferases or PAPS-independent aryl sulfotransferases such as those from Desulfitobacterium hafniense, or chemically using SO3 complexes. Both approaches were tested with six selected phenolic acids (2-hydroxyphenylacetic acid (2-HPA), 3-hydroxyphenylacetic acid (3-HPA), 4-hydroxyphenylacetic acid (4-HPA), 3,4-dihydroxyphenylacetic acid (DHPA), 3-(4-hydroxyphenyl)propionic acid (4-HPP), and 3,4-dihydroxyphenylpropionic acid (DHPP)) to create a library of sulfated metabolites of phenolic acids. The sulfates of 3-HPA, 4-HPA, 4-HPP, DHPA, and DHPP were all obtained by the methods of chemical synthesis. In contrast, the enzymatic sulfation of monohydroxyphenolic acids failed probably due to enzyme inhibition, whereas the same reaction was successful for dihydroxyphenolic acids (DHPA and DHPP). Special attention was also paid to the counterions of the sulfates, a topic often poorly reported in synthetic works. The products obtained will serve as authentic analytical standards in metabolic studies and to determine their biological activity. Full article
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15 pages, 1738 KiB  
Article
Biotransformation of Waste Bile Acids: A New Possible Sustainable Approach to Anti-Fungal Molecules for Crop Plant Bioprotection?
by Alessandro Grandini, Daniela Summa, Stefania Costa, Raissa Buzzi, Elena Tamburini, Gianni Sacchetti and Alessandra Guerrini
Int. J. Mol. Sci. 2022, 23(8), 4152; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23084152 - 08 Apr 2022
Cited by 4 | Viewed by 2335
Abstract
Phytopathogenic fungi are among the main causes of productivity losses in agriculture. To date, synthetic chemical pesticides, such as hydroxyanilides, anilinopyrimidines and azole derivatives, represent the main treatment tools for crop plant defence. However, the large and uncontrolled use of these substances has [...] Read more.
Phytopathogenic fungi are among the main causes of productivity losses in agriculture. To date, synthetic chemical pesticides, such as hydroxyanilides, anilinopyrimidines and azole derivatives, represent the main treatment tools for crop plant defence. However, the large and uncontrolled use of these substances has evidenced several side effects, namely the resistance to treatments, environmental damage and human health risks. The general trend is to replace chemicals with natural molecules in order to reduce these side effects. Moreover, the valorisation of agri-food industry by-products through biotransformation processes represents a sustainable alternative to chemical synthesis in several sectors. This research is aimed at comparing the anti-phytopathogenic activity of waste bovine and porcine bile with secosteroids obtained by biotransformation of bile acids with Rhodococcus strains. The ultimate goal is to apply these natural products on food crops affected by phytopathogenic fungi. Full article
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16 pages, 1062 KiB  
Article
Biotransformation of the Phenolic Constituents from Licorice and Cytotoxicity Evaluation of Their Metabolites
by Yina Xiao, Fubo Han and Ik-Soo Lee
Int. J. Mol. Sci. 2021, 22(18), 10109; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221810109 - 18 Sep 2021
Cited by 8 | Viewed by 1826
Abstract
Biotransformation of four bioactive phenolic constituents from licorice, namely licoisoflavanone (1), glycyrrhisoflavone (2), echinatin (3), and isobavachalcone (4), was performed by the selected fungal strain Aspergillus niger KCCM 60332, leading to the isolation of seventeen [...] Read more.
Biotransformation of four bioactive phenolic constituents from licorice, namely licoisoflavanone (1), glycyrrhisoflavone (2), echinatin (3), and isobavachalcone (4), was performed by the selected fungal strain Aspergillus niger KCCM 60332, leading to the isolation of seventeen metabolites (521). Structures of the isolated compounds were determined on the basis of extensive spectroscopic methods, twelve of which (57, 1017 and 19) have been previously undescribed. A series of reactions including hydroxylation, hydrogenation, epoxidation, hydrolysis, reduction, cyclization, and alkylation was observed in the biotransformation process. All compounds were tested for their cytotoxic activities against three different human cancer cell lines including A375P, MCF-7, and HT-29. Compounds 1 and 12 exhibited most considerable cytotoxic activities against all the cell lines investigated, while compounds 2 and 4 were moderately cytotoxic. These findings will contribute to expanding the chemical diversity of phenolic compounds, and compounds 1 and 12 may serve as leads for the development of potential cancer chemopreventive agents. Full article
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9 pages, 1449 KiB  
Article
Glycosylation of Ganoderic Acid G by Bacillus Glycosyltransferases
by Jiumn-Yih Wu, Hsiou-Yu Ding, Tzi-Yuan Wang, Yun-Rong Zhang and Te-Sheng Chang
Int. J. Mol. Sci. 2021, 22(18), 9744; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22189744 - 09 Sep 2021
Cited by 4 | Viewed by 1637
Abstract
Ganoderma lucidum is a medicinal fungus abundant in triterpenoids, its primary bioactive components. Although numerous Ganoderma triterpenoids have already been identified, rare Ganoderma triterpenoid saponins were recently discovered. To create novel Ganoderma saponins, ganoderic acid G (GAG) was selected for biotransformation using four [...] Read more.
Ganoderma lucidum is a medicinal fungus abundant in triterpenoids, its primary bioactive components. Although numerous Ganoderma triterpenoids have already been identified, rare Ganoderma triterpenoid saponins were recently discovered. To create novel Ganoderma saponins, ganoderic acid G (GAG) was selected for biotransformation using four Bacillus glycosyltransferases (GTs) including BtGT_16345 from the Bacillus thuringiensis GA A07 strain and three GTs (BsGT110, BsUGT398, and BsUGT489) from the Bacillus subtilis ATCC 6633 strain. The results showed that BsUGT489 catalyzed the glycosylation of GAG to GAG-3-o-β-glucoside, while BsGT110 catalyzed the glycosylation of GAG to GAG-26-o-β-glucoside, which showed 54-fold and 97-fold greater aqueous solubility than that of GAG, respectively. To our knowledge, these two GAG saponins are new compounds. The glycosylation specificity of the four Bacillus GTs highlights the possibility of novel Ganoderma triterpenoid saponin production in the future. Full article
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14 pages, 1548 KiB  
Article
Microbial Conjugation Studies of Licochalcones and Xanthohumol
by Fubo Han, Yina Xiao and Ik-Soo Lee
Int. J. Mol. Sci. 2021, 22(13), 6893; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22136893 - 26 Jun 2021
Cited by 6 | Viewed by 2152
Abstract
Microbial conjugation studies of licochalcones (14) and xanthohumol (5) were performed by using the fungi Mucor hiemalis and Absidia coerulea. As a result, one new glucosylated metabolite was produced by M. hiemalis whereas four new and [...] Read more.
Microbial conjugation studies of licochalcones (14) and xanthohumol (5) were performed by using the fungi Mucor hiemalis and Absidia coerulea. As a result, one new glucosylated metabolite was produced by M. hiemalis whereas four new and three known sulfated metabolites were obtained by transformation with A. coerulea. Chemical structures of all the metabolites were elucidated on the basis of 1D-, 2D-NMR and mass spectroscopic data analyses. These results could contribute to a better understanding of the metabolic fates of licochalcones and xanthohumol in mammalian systems. Although licochalcone A 4′-sulfate (7) showed less cytotoxic activity against human cancer cell lines compared to its substrate licochalcone A, its activity was fairly retained with the IC50 values in the range of 27.35–43.07 μM. Full article
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17 pages, 3819 KiB  
Article
Bioconversion of Callus-Produced Precursors to Silymarin Derivatives in Silybum marianum Leaves for the Production of Bioactive Compounds
by Dina Gad, Hamed El-Shora, Daniele Fraternale, Elisa Maricchiolo, Andrea Pompa and Karl-Josef Dietz
Int. J. Mol. Sci. 2021, 22(4), 2149; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22042149 - 21 Feb 2021
Cited by 3 | Viewed by 2633
Abstract
The present study aimed to investigate the enzymatic potential of Silybum marianum leaves to bioconvert phenolic acids produced in S. marianum callus into silymarin derivatives as chemopreventive agent. Here we demonstrate that despite the fact that leaves of S. marianum did not accumulate [...] Read more.
The present study aimed to investigate the enzymatic potential of Silybum marianum leaves to bioconvert phenolic acids produced in S. marianum callus into silymarin derivatives as chemopreventive agent. Here we demonstrate that despite the fact that leaves of S. marianum did not accumulate silymarin themselves, expanding leaves had the full capacity to convert di-caffeoylquinic acid to silymarin complex. This was proven by HPLC separations coupled with electrospray ionization mass spectrometry (ESI-MS) analysis. Soaking the leaf discs with S. marianum callus extract for different times revealed that silymarin derivatives had been formed at high yield after 16 h. Bioconverted products displayed the same retention time and the same mass spectra (MS or MS/MS) as standard silymarin. Bioconversion was achieved only when using leaves of a specific age, as both very young and old leaves failed to produce silymarin from callus extract. Only medium leaves had the metabolic capacity to convert callus components into silymarin. The results revealed higher activities of enzymes of the phenylpropanoid pathway in medium leaves than in young and old leaves. It is concluded that cotyledon-derived callus efficiently produces compounds that can be bio-converted to flavonolignans in leaves tissue of S. marianum. Full article
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Review

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15 pages, 1009 KiB  
Review
Role of Arachidonic Acid and Its Metabolites in the Biological and Clinical Manifestations of Idiopathic Nephrotic Syndrome
by Stefano Turolo, Alberto Edefonti, Alessandra Mazzocchi, Marie Louise Syren, William Morello, Carlo Agostoni and Giovanni Montini
Int. J. Mol. Sci. 2021, 22(11), 5452; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115452 - 21 May 2021
Cited by 14 | Viewed by 3895
Abstract
Studies concerning the role of arachidonic acid (AA) and its metabolites in kidney disease are scarce, and this applies in particular to idiopathic nephrotic syndrome (INS). INS is one of the most frequent glomerular diseases in childhood; it is characterized by T-lymphocyte dysfunction, [...] Read more.
Studies concerning the role of arachidonic acid (AA) and its metabolites in kidney disease are scarce, and this applies in particular to idiopathic nephrotic syndrome (INS). INS is one of the most frequent glomerular diseases in childhood; it is characterized by T-lymphocyte dysfunction, alterations of pro- and anti-coagulant factor levels, and increased platelet count and aggregation, leading to thrombophilia. AA and its metabolites are involved in several biological processes. Herein, we describe the main fields where they may play a significant role, particularly as it pertains to their effects on the kidney and the mechanisms underlying INS. AA and its metabolites influence cell membrane fluidity and permeability, modulate platelet activity and coagulation, regulate lymphocyte activity and inflammation, preserve the permeability of the glomerular barrier, influence podocyte physiology, and play a role in renal fibrosis. We also provide suggestions regarding dietary measures that are able to prevent an imbalance between arachidonic acid and its parental compound linoleic acid, in order to counteract the inflammatory state which characterizes numerous kidney diseases. On this basis, studies of AA in kidney disease appear as an important field to explore, with possible relevant results at the biological, dietary, and pharmacological level, in the final perspective for AA to modulate INS clinical manifestations. Full article
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