Fungal Biotransformations in Pharmaceutical Sciences

Hüttel, Wolfgang; Hoffmeister, Dirk

doi:10.1007/978-3-642-11458-8_14

Cited by 11 publications

(7 citation statements)

References 65 publications

(7 reference statements)

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“…On the other hand, mucoralean fungi have been used for centuries to ferment traditional Asian and African food [5] and are utilized for the production of several varieties of European cheese [2]. As producers of a broad spectrum of enzymes, Mucorales are used in biotechnology for the biotransformation of several medically and pharmaceutically important compounds such as steroids and terpenoids [1,2,6]. Our understanding of Mucorales biology has severely suffered from a largely unresolved taxonomy.…”

Section: Introductionmentioning

confidence: 99%

Updates on the Taxonomy of Mucorales with an Emphasis on Clinically Important Taxa

Walther

Wagner

Kurzai

2019

JoF

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Fungi of the order Mucorales colonize all kinds of wet, organic materials and represent a permanent part of the human environment. They are economically important as fermenting agents of soybean products and producers of enzymes, but also as plant parasites and spoilage organisms. Several taxa cause life-threatening infections, predominantly in patients with impaired immunity. The order Mucorales has now been assigned to the phylum Mucoromycota and is comprised of 261 species in 55 genera. Of these accepted species, 38 have been reported to cause infections in humans, as a clinical entity known as mucormycosis. Due to molecular phylogenetic studies, the taxonomy of the order has changed widely during the last years. Characteristics such as homothallism, the shape of the suspensors, or the formation of sporangiola are shown to be not taxonomically relevant. Several genera including Absidia, Backusella, Circinella, Mucor, and Rhizomucor have been amended and their revisions are summarized in this review. Medically important species that have been affected by recent changes include Lichtheimia corymbifera, Mucor circinelloides, and Rhizopus microsporus. The species concept of Rhizopus arrhizus (syn. R. oryzae) is still a matter of debate. Currently, species identification of the Mucorales is best performed by sequencing of the internal transcribed spacer (ITS) region. Ecologically, the Mucorales represent a diverse group but for the majority of taxa, the ecological role and the geographic distribution remain unknown. Understanding the biology of these opportunistic fungal pathogens is a prerequisite for the prevention of infections, and, consequently, studies on the ecology of the Mucorales are urgently needed.

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Section: Introductionmentioning

confidence: 99%

Updates on the Taxonomy of Mucorales with an Emphasis on Clinically Important Taxa

Walther

Wagner

Kurzai

2019

JoF

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“…Our recent study demonstrated that the addition of ASA in the Gl cultivation substrate stimulates the production of more or new bioactive compounds, mainly the polysaccharides, B-methyl glucopyranoside, DL-arabinitol and ribitol, in comparison with the conventional extract (no ASA) [ 63 ]. This pattern might be the result of biotransformation processes that occur when fungal enzymes catalyze chemical modifications of a compound [ 64 ]. From a biomedical point of view, we focused on the acetylsalicylic acid, a non-steroidal anti-inflammatory drug approved for the treatment of pain and fever, that has also been included as a secondary prevention in stroke treatment and cardiovascular disease at low dose.…”

Section: Discussionmentioning

confidence: 99%

Mexican Ganoderma Lucidum Extracts Decrease Lipogenesis Modulating Transcriptional Metabolic Networks and Gut Microbiota in C57BL/6 Mice Fed with a High-Cholesterol Diet

et al. 2020

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Prevention of hyperlipidemia and associated diseases is a health priority. Natural products, such as the medicinal mushroom Ganoderma lucidum (Gl), have demonstrated hypocholesterolemic, prebiotic and antidiabetic properties. However, the underlying transcriptomic mechanisms by which Gl exerts bioactivities are not completely understood. We report a comprehensive hepatic and renal transcriptome profiling of C57BL/6 mice under the consumption of a high-cholesterol diet and two standardized Gl extracts obtained from basidiocarps cultivated on conventional substrate (Gl-1) or substrate containing acetylsalicylic acid (ASA; Gl-2). We showed that Gl extracts modulate relevant metabolic pathways involving the restriction of lipid biosynthesis and the enrichment of lipid degradation and secretion. The Gl-2 extract exerts a major modulation over gene expression programs showing the highest similarity with simvastatin druggable-target-genes and these are enriched more in processes related to human obesity alterations in the liver. We further show a subset of Gl-modulated genes correlated with Lactobacillus enrichment and the reduction of circulating cholesterol-derived fats. Moreover, Gl extracts induce a significant decrease of macrophage lipid storage, which occurs concomitantly with the down-modulation of Fasn and Elovl6. Collectively, this evidence suggests a new link between Gl hypocholesterolemic and prebiotic activity, revealing thereby that standardized Mexican Gl extracts are a novel transcriptome modulator to prevent metabolic disorders associated with hypercholesterolemia.

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“…Fungi-mediated biotransformations allow production of compounds with high regioand stereoselectivity through reduction, oxidation, epoxidation, hydrogenation, hydrolysis, amination, acylation, glucosylation, epoxidation, hydration, methylation and hydroxylation by cytochrome P450 enzymes, especially regarding steroid conversion [24][25][26]. Moreover, the valuable characteristic of a fungi-based approach is the complexity of their metabolic abilities, allowing for xenobiotic degradation that is partially reminiscent of mammalian metabolism [26]. Diao et al reported that hydroxylation of 3-n-butylphthalide, a saturated analogue of 3-n-butylidenephthalide, was the main metabolic route in humans, and that this hydroxylation occurred on the side chain instead of the relatively stable benzene ring.…”

Section: Introductionmentioning

confidence: 99%

Microbial Synthesis and Evaluation of Fungistatic Activity of 3-Butyl-3-hydroxyphthalide, the Mammalian Metabolite of 3-n-Butylidenephthalide

Gach

Olejniczak

Krężel

et al. 2021

IJMS

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Phthalides are bioactive compounds that naturally occur in the family Apiaceae. Considering their potentially versatile applications, it is desirable to determine their physical properties, activity and metabolic pathways. This study aimed to examine the utility of whole-cell biocatalysts for obtaining 3-butyl-3-hydroxyphthalide, which is the metabolite formulated during mammalian metabolism of 3-n-butylidenephthalide. We performed transformations using 10 strains of fungi, five of which efficiently produced 3-butyl-3-hydroxyphthalide. The product yield, determined by high-performance liquid chromatography, reached 97.6% when Aspergillus candidus AM 386 was used as the biocatalyst. Increasing the scale of the process resulted in isolation yields of 29–45% after purification via reversed-phase thin layer chromatography, depending on the strain of the microorganism used. We proposed different mechanisms for product formation; however, hydration of 3-n-butylidenephthalide seems to be the most probable. Additionally, all phthalides were tested against clinical strains of Candida albicans using the microdilution method. Two phthalides showed a minimum inhibitory concentration, required to inhibit the growth of 50% of organisms, below 50 µg/mL. The 3-n-butylidenephthalide metabolite was generally inactive, and this feature in combination with its low lipophilicity suggests its involvement in the detoxification pathway. The log P value of tested compounds was in the range of 2.09–3.38.

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Fungal Biotransformations in Pharmaceutical Sciences

Cited by 11 publications

References 65 publications

Updates on the Taxonomy of Mucorales with an Emphasis on Clinically Important Taxa

Updates on the Taxonomy of Mucorales with an Emphasis on Clinically Important Taxa

Mexican Ganoderma Lucidum Extracts Decrease Lipogenesis Modulating Transcriptional Metabolic Networks and Gut Microbiota in C57BL/6 Mice Fed with a High-Cholesterol Diet

Microbial Synthesis and Evaluation of Fungistatic Activity of 3-Butyl-3-hydroxyphthalide, the Mammalian Metabolite of 3-n-Butylidenephthalide

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