Biosynthesis Of Fungal Metabolites Research Articles

Vacuolal and Peroxisomal Calcium Ion Transporters in Yeasts and Fungi: Key Role in the Translocation of Intermediates in the Biosynthesis of Fungal Metabolites.

Highlights The intracellular calcium content plays a key role in the expression of genes involved in the biosynthesis and secretion of fungal metabolites.The cytosolic calcium concentration in fungi is maintained by influx through the cell membrane and by release from store organelles.Some MSF transporters, e.g., PenV of Penicillium chrysogenum and CefP of Acremonium chrysogenum belong to the TRP calcium ion channels.A few of the numerous calcium ion transporters existing in organelles of different filamentous fungi have been characterized at the functional and subcellular localization levels.The cytosolic calcium signal seems to be transduced by the calcitonin/calcineurin cascade controlling the expression of many fungal genes. The intracellular calcium content in fungal cells is influenced by a large number of environmental and nutritional factors. Sharp changes in the cytosolic calcium level act as signals that are decoded by the cell gene expression machinery, resulting in several physiological responses, including differentiation and secondary metabolites biosynthesis. Expression of the three penicillin biosynthetic genes is regulated by calcium ions, but there is still little information on the role of this ion in the translocation of penicillin intermediates between different subcellular compartments. Using advanced information on the transport of calcium in organelles in yeast as a model, this article reviews the recent progress on the transport of calcium in vacuoles and peroxisomes and its relation to the translocation of biosynthetic intermediates in filamentous fungi. The Penicillium chrysogenum PenV vacuole transporter and the Acremonium chrysogenum CefP peroxisomal transporter belong to the transient receptor potential (TRP) class CSC of calcium ion channels. The PenV transporter plays an important role in providing precursors for the biosynthesis of the tripeptide δ-(-α-aminoadipyl-L-cysteinyl-D-valine), the first intermediate of penicillin biosynthesis in P. chrysogenum. Similarly, CefP exerts a key function in the conversion of isopenicillin N to penicillin N in peroxisomes of A. chrysogenum. These TRP transporters are different from other TRP ion channels of Giberella zeae that belong to the Yvc1 class of yeast TRPs. Recent advances in filamentous fungi indicate that the cytosolic calcium concentration signal is connected to the calcitonin/calcineurin signal transduction cascade that controls the expression of genes involved in the subcellular translocation of intermediates during fungal metabolite biosynthesis. These advances open new possibilities to enhance the expression of important biosynthetic genes in fungi.

Rapid reconstitution of biosynthetic machinery for fungal metabolites in Aspergillus oryzae: total biosynthesis of aflatrem.

Reconstitution of the biosynthetic machinery for fungal secondary metabolites in Aspergillus oryzae provides an opportunity both for stepwise determination of the biosynthetic pathways and the total biosynthesis of fungal natural products. However, to maximize the utility of the reconstitution system, a simple and rapid strategy for the introduction of heterologous genes into A. oryzae is required. In this study, we demonstrated an effective method for introducing multiple genes involved in the biosynthesis of fungal metabolites by using the expression vectors pUARA2 and pUSA2, each of which contains two cloning sites. The successful introduction of all the aflatrem biosynthetic genes (seven genes in total) after two rounds of transformation enabled the total biosynthesis of aflatrem. This rapid reconstitution strategy will facilitate the functional analysis of the biosynthetic machinery of fungal metabolites.

Biosynthesis of fungal metabolites: asperlactone and its relationship to other metabolites of Aspergillus melleus

The biosynthesis of asperlactone (5) from [1,2-13C2]-, [2-13C, 2-2H3]- and [2H3]-acetate has been investigated. The pattern of incorporation of intact acetate units was checked with [1,2-13C2]acetate. The presence in the 13C n.m.r. spectrum of a two-bond coupling (J 7.5 Hz) between C-2 and C-8 was verified by sine bell resolution enhancement of the Free Induction Decay. Therefore these two carbons, originally Joined in a C2 unit derived from acetate, become separated by a rearrangement, and so finish in a 1,3 relationship. The carbon skeleton is therefore built up in identical fashion to that of the co-metabolite aspyrone (1). The retention of two acetate-derived hydrogens from [2-13C, 2-2H3]acetate at C-7 rules out the intermediacy of structures in which this carbon forms part of an aromatic ring. This experiment also confirms that C-10 can retain three deuterium atoms and so is a chain starter methyl group. The overall retention of acetate hydrogen was determined by a 2H n.m.r. study of [2-2H3]acetate-enriched asperlactone. To account for these results a biosynthetic model involving partially reduced polyketone intermediates is suggested (Scheme 4). Mechanistically feasible decarboxylation and rearrangement steps are followed by stereospecific opening of an epoxide ring to generate aspyrone (1) or asperlactone (5). The possible derivation of the aromatic co-metabolites, mellein (2) and hydroxymellein (3), from the same intermediate (10), generated on the same polyketide synthase, is discussed.

The biosynthesis of fungal metabolites. Part VIII. Identification of N-benzoyl-L-phenylalanyl-L-phenylalaninol acetate, a metabolite of Aspergillus glaucus.

Asperglaucide, a metabolite of Aspergillus glaucus, is shown by spectroscopoc methods, chemical degradation, and synthesis to be N-benzoyl-L-phenylalanyl-L-phenylalaninol acetate (II)

The biosynthesis of fungal metabolites. Part IX. Sclerin: feedings with [1,2-13C]acetate and[methyl-13C]methionine.

The 13C n.m.r. spectra of methyl 2-(3-hydroxy-2-methoxycarbonyl-4,5,6-trimethylphenyl)propionate (II) derived from the fungal metabolite sclerin (I) enriched with 13C from [1,2-13C]acetate or from [methyl-13C]-methionine, establish that the metabolite is derived from two β-ketide precursors with the introduction of three C-methyl groups from methionine.

The biosynthesis of fungal metabolites. Part VI. Structures and biosynthesis of some minor metabolites from variant strains of Aspergillus variecolor

New minor metabolites from variant strains of A. variecolor are shown to be (1R,2S)-8-[(2S)-2,3-dihydroxy-3-methylbutyl]-2,3-dihydro-1,11-dihydroxy-2-isopropenyl-5-methyl-(III), (1R,2S)-2,3-dihydro-1,11-dihydroxy-8-[(2S)-2-hydroxy-3-methoxy-3-methylbutyl]-2-isopropenyl-5-methyl-(IV), 1,2-trans-1-acetoxy-8-(2,3-epoxy-1-hydroxy-3-methylbutyl)-2,3-dihydro-11-hydroxy-2-isopropenyl-5-methyl-(V), 1,2-trans-1-acetoxy-8-(2,3-epoxy-1-methoxy-3-methylbutyl)-2,3-dihydro-11-hydroxy-2-isopropenyl-5-methyl-(VI), and 1,2-cis-2,3-dihydro-1,11-dihydroxy-2-isopropenyl-5-methyl-10-(3-methylbut-2-enyl)-pyrano[3,2-a]xanthen-12(1H)-one (X), 1,10-dihydroxy-6-methoxy-8-methyl-2-(3-methylbut-2-enyl)-7-(3-methylbut-2-enyloxy)-dibenz[b,e]oxepin-11(6H)-one (XVIII), and 1,12a-dihydro-6,8-dihydroxy-1-(1-hydroxy-1-methylethyl)-4-methyl-9-(2-hydroxy-3-methylbut-3-enyl)[1]benzopyrano[4,5-bc][1]benzoxepin-7(2H)-one (XXI). A biogenetic relationship is suggested which explains the co-occurrence of these compounds with other metabolites of known structures.

The biosynthesis of fungal metabolites. Part IV. Tajixanthone: 13C nuclear magnetic resonance spectrum and feedings with [1-13C]- and [2-13C]-acetate

The 13C N.m.r. spectra of tajixanthone (I) and related compounds (VI)–(XV) have been completely assigned Spectra of tajixanthone derived by incorporation of [1-13C]- and [2-13C]-acetate show patterns of enrichment consistent with a biosynthetic pathway in which the xanthone arises by ring scission of 1,8-dihydroxy-3-methyl-9-anthrone (chrysophanol anthrone), derived on a β-ketide pathway, with introduction of C- and O-prenyl units from mevalonate.

The biosynthesis of fungal metabolites. Part III. Structure of shamixanthone and tajixanthone, metabolites of Aspergillus variecolor

The structures of shamixanthone and tajixanthone, optically active metabolites of Aspergillus variecolor, are shown to be (1R,2S)-1,11-dihydroxy-2-isopropenyl-5-methyl-8-(3-methylbut-2-enyl)-(IV) and (1R,2S)-8-[(2S)-2,3-epoxy-3-methylbutyl]-1,11-dihydroxy-2-isopropenyl-5-methyl-2,3-dihydro-1H-pyrano[3,2-a]xanthen-12-one (V) respectively. These structures were established by detailed analyses of the 1H and 13C n.m.r. spectra of the metabolites and their derived compounds as well as by chemical degradation of the substituted dihydrobenzopyran system. The absolute configurations were assigned by application of the Horeau asymmetric synthesis.

Studies in the biosynthesis of fungal metabolites. 5. The utilization of sulphur-containing amino acids as pencillin side-chain precursors.

Research Article| June 01 1963 Studies in the biosynthesis of fungal metabolites. 5. The utilization of sulphur-containing amino acids as pencillin side-chain precursors E ALBU; E ALBU Search for other works by this author on: This Site PubMed Google Scholar R THOMAS R THOMAS Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1963) 87 (3): 648–652. https://doi.org/10.1042/bj0870648 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation E ALBU, R THOMAS; Studies in the biosynthesis of fungal metabolites. 5. The utilization of sulphur-containing amino acids as pencillin side-chain precursors. Biochem J 1 June 1963; 87 (3): 648–652. doi: https://doi.org/10.1042/bj0870648 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1963 The Biochemical Society1963 Article PDF first page preview Close Modal You do not currently have access to this content.

Studies in the biosynthesis of fungal metabolites. 4. Alternariol monomethyl ether and its relation to other phenolic metabolites of Alternaria tenuis.

Studies in the biosynthesis of fungal metabolites. 4. Alternariol monomethyl ether and its relation to other phenolic metabolites of Alternaria tenuis.

Studies in the biosynthesis of fungal metabolites. 2. The biosynthesis of alternariol and its relation to other fungal phenols.

Studies in the biosynthesis of fungal metabolites. 2. The biosynthesis of alternariol and its relation to other fungal phenols.

Studies in the biosynthesis of fungal metabolites. 3. The biosynthesis of fungal perinaphthenones.

Studies in the biosynthesis of fungal metabolites. 3. The biosynthesis of fungal perinaphthenones.

Studies in the biosynthesis of fungal metabolites. The biosynthesis of palitantin.

Research Article| October 01 1960 Studies in the biosynthesis of fungal metabolites. The biosynthesis of palitantin P. Chaplen; P. Chaplen 1Department of Biochemistry, London School of Hygiene and Tropical Medicine, University of London Search for other works by this author on: This Site PubMed Google Scholar R. Thomas R. Thomas 1Department of Biochemistry, London School of Hygiene and Tropical Medicine, University of London Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1960) 77 (1): 91–96. https://doi.org/10.1042/bj0770091 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation P. Chaplen, R. Thomas; Studies in the biosynthesis of fungal metabolites. The biosynthesis of palitantin. Biochem J 1 October 1960; 77 (1): 91–96. doi: https://doi.org/10.1042/bj0770091 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1960 CAMBRIDGE UNIVERSITY PRESS1960 Article PDF first page preview Close Modal You do not currently have access to this content.