Author
Geoffrey Turner
Other affiliations: University of Nebraska–Lincoln, University of Maryland, Baltimore
Bio: Geoffrey Turner is an academic researcher from University of Sheffield. The author has contributed to research in topics: Aspergillus nidulans & Aspergillus fumigatus. The author has an hindex of 23, co-authored 47 publications receiving 5226 citations. Previous affiliations of Geoffrey Turner include University of Nebraska–Lincoln & University of Maryland, Baltimore.
Papers
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TL;DR: Questions are addressed, including which evolutionary pressures led to gene clustering, why closely related species produce different profiles of secondary metabolites, and whether fungal genomics will accelerate the discovery of new pharmacologically active natural products.
Abstract: Much of natural product chemistry concerns a group of compounds known as secondary metabolites. These low-molecular-weight metabolites often have potent physiological activities. Digitalis, morphine and quinine are plant secondary metabolites, whereas penicillin, cephalosporin, ergotrate and the statins are equally well known fungal secondary metabolites. Although chemically diverse, all secondary metabolites are produced by a few common biosynthetic pathways, often in conjunction with morphological development. Recent advances in molecular biology, bioinformatics and comparative genomics have revealed that the genes encoding specific fungal secondary metabolites are clustered and often located near telomeres. In this review, we address some important questions, including which evolutionary pressures led to gene clustering, why closely related species produce different profiles of secondary metabolites, and whether fungal genomics will accelerate the discovery of new pharmacologically active natural products.
1,488 citations
Washington University in St. Louis1, J. Craig Venter Institute2, Wellcome Trust Sanger Institute3, University of Manchester4, Complutense University of Madrid5, Tohoku University6, University of Nottingham7, Tulane University8, University of Kentucky9, Max Planck Society10, Spanish National Research Council11, University of Salamanca12, University of São Paulo13, Innsbruck Medical University14, University of Wisconsin-Madison15, University of Tokyo16, Nagoya University17, National Institute of Advanced Industrial Science and Technology18, Pasteur Institute19, University of Texas MD Anderson Cancer Center20, University of Idaho21, University of Lausanne22, University of Göttingen23, Tokyo University of Agriculture and Technology24, University of Sheffield25, Broad Institute26
TL;DR: The Af293 genome sequence provides an unparalleled resource for the future understanding of this remarkable fungus and revealed temperature-dependent expression of distinct sets of genes, as well as 700 A. fumigatus genes not present or significantly diverged in the closely related sexual species Neosartorya fischeri, many of which may have roles in the pathogenicity phenotype.
Abstract: Aspergillus fumigatus is exceptional among microorganisms in being both a primary and opportunistic pathogen as well as a major allergen. Its conidia production is prolific, and so human respiratory tract exposure is almost constant. A. fumigatus is isolated from human habitats and vegetable compost heaps. In immunocompromised individuals, the incidence of invasive infection can be as high as 50% and the mortality rate is often about 50% (ref. 2). The interaction of A. fumigatus and other airborne fungi with the immune system is increasingly linked to severe asthma and sinusitis. Although the burden of invasive disease caused by A. fumigatus is substantial, the basic biology of the organism is mostly obscure. Here we show the complete 29.4-megabase genome sequence of the clinical isolate Af293, which consists of eight chromosomes containing 9,926 predicted genes. Microarray analysis revealed temperature-dependent expression of distinct sets of genes, as well as 700 A. fumigatus genes not present or significantly diverged in the closely related sexual species Neosartorya fischeri, many of which may have roles in the pathogenicity phenotype. The Af293 genome sequence provides an unparalleled resource for the future understanding of this remarkable fungus.
1,356 citations
DSM1, Delft University of Technology2, University of Nottingham3, Technical University of Denmark4, Wageningen University and Research Centre5, University of Sheffield6, Utrecht University7, Biomax Informatics AG8, CLC bio9, University of Liverpool10, Ghent University11, University of Manchester12, University of Provence13, University of Groningen14, Pasteur Institute15, University of Amsterdam16, University of Angers17, Leiden University18, Radboud University Nijmegen19, University of Szeged20
TL;DR: The filamentous fungus Aspergillus niger is widely exploited by the fermentation industry for the production of enzymes and organic acids, particularly citric acid, and the sequenced genome revealed a large number of major facilitator superfamily transporters and fungal zinc binuclear cluster transcription factors.
Abstract: The filamentous fungus Aspergillus niger is widely exploited by the fermentation industry for the production of enzymes and organic acids, particularly citric acid. We sequenced the 33.9-megabase genome of A. niger CBS 513.88, the ancestor of currently used enzyme production strains. A high level of synteny was observed with other aspergilli sequenced. Strong function predictions were made for 6,506 of the 14,165 open reading frames identified. A detailed description of the components of the protein secretion pathway was made and striking differences in the hydrolytic enzyme spectra of aspergilli were observed. A reconstructed metabolic network comprising 1,069 unique reactions illustrates the versatile metabolism of A. niger. Noteworthy is the large number of major facilitator superfamily transporters and fungal zinc binuclear cluster transcription factors, and the presence of putative gene clusters for fumonisin and ochratoxin A synthesis.
1,161 citations
TL;DR: It is concluded that the gene Afu8g00170, named ftmA, encodes the NRPS brevianamide synthetase, the precursor of a variety of fungal prenylated alkaloids with biological activity, including fumitremorgins A, B and C and tryprostatin B.
Abstract: A gene encoding a putative dimodular nonribosomal peptide synthetase (NRPS) was identified within a gene cluster of Aspergillus fumigatus, a species reported to produce fumitremorgins and other prenylated alkaloids. The gene was deleted and overexpressed in the genome reference strain Af293, and was also expressed in the naive host Aspergillus nidulans, which lacks the equivalent gene cluster. While neither fumitremorgins nor the dipeptide brevianamide F (cyclo-L-Trp-L-Pro), an early intermediate, were detected in wild-type and deletion strains of A. fumigatus, brevianamide F accumulated in fungal cultures following increased expression of the NRPS gene in both A. fumigatus and A. nidulans. We conclude that the gene Afu8g00170, named ftmA, encodes the NRPS brevianamide synthetase. Brevianamide F is the precursor of a variety of fungal prenylated alkaloids with biological activity, including fumitremorgins A, B and C and tryprostatin B.
165 citations
TL;DR: Evidence is presented that the PKS/NRPS gene psoA is required for the biosynthesis of pseurotin A, a compound with an unusual heterospirocyclic γ‐lactam structure that is reported to be a competitive inhibitor of chitin synthase and an inducer of nerve‐cell proliferation.
Abstract: The genome sequence of Aspergillus fumigatus revealed the presence of a single hybrid polyketide synthase–non-ribosomal peptide synthetase (PKS/NRPS) gene that is present within a cluster of five genes suggestive of its involvement in secondary metabolism. Here, we present evidence that it is required for the biosynthesis of pseurotin A, a compound with an unusual heterospirocyclic γ-lactam structure. We have confirmed that the genome reference strain A. fumigatus Af293 produces pseurotin A, a compound previously reported to be a competitive inhibitor of chitin synthase and an inducer of nerve-cell proliferation. Deletion or overexpression of the PKS/NRPS gene psoA in A. fumigatus leads to the absence or accumulation of pseurotin A, respectively; this indicates that this gene is essential for the biosynthesis of pseurotin A. It is likely that the first product of psoA is converted to pseurotin A by the products of other genes in this cluster.
143 citations
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10 Dec 2007
TL;DR: The experiments on both rice and human genome sequences demonstrate that EVM produces automated gene structure annotation approaching the quality of manual curation.
Abstract: EVidenceModeler (EVM) is presented as an automated eukaryotic gene structure annotation tool that reports eukaryotic gene structures as a weighted consensus of all available evidence. EVM, when combined with the Program to Assemble Spliced Alignments (PASA), yields a comprehensive, configurable annotation system that predicts protein-coding genes and alternatively spliced isoforms. Our experiments on both rice and human genome sequences demonstrate that EVM produces automated gene structure annotation approaching the quality of manual curation.
1,528 citations
TL;DR: Questions are addressed, including which evolutionary pressures led to gene clustering, why closely related species produce different profiles of secondary metabolites, and whether fungal genomics will accelerate the discovery of new pharmacologically active natural products.
Abstract: Much of natural product chemistry concerns a group of compounds known as secondary metabolites. These low-molecular-weight metabolites often have potent physiological activities. Digitalis, morphine and quinine are plant secondary metabolites, whereas penicillin, cephalosporin, ergotrate and the statins are equally well known fungal secondary metabolites. Although chemically diverse, all secondary metabolites are produced by a few common biosynthetic pathways, often in conjunction with morphological development. Recent advances in molecular biology, bioinformatics and comparative genomics have revealed that the genes encoding specific fungal secondary metabolites are clustered and often located near telomeres. In this review, we address some important questions, including which evolutionary pressures led to gene clustering, why closely related species produce different profiles of secondary metabolites, and whether fungal genomics will accelerate the discovery of new pharmacologically active natural products.
1,488 citations
Broad Institute1, J. Craig Venter Institute2, Stanford University3, Oregon Health & Science University4, University of Glasgow5, Genetic Information Research Institute6, Institut Universitaire de France7, University of Kentucky8, University of Nebraska–Lincoln9, University of Göttingen10, Pasteur Institute11, University of São Paulo12, Texas A&M University13, Wellcome Trust Sanger Institute14, John Innes Centre15, University of Wisconsin-Madison16, Max Planck Society17, University of Oregon18, University of Nottingham19, Spanish National Research Council20, Ohio State University21, University of Georgia22, Tokyo Institute of Technology23, National Institute of Advanced Industrial Science and Technology24, George Washington University25, University of Manchester26, University of Liverpool27, University of Melbourne28, Karlsruhe Institute of Technology29, University of Idaho30
TL;DR: The aspergilli comprise a diverse group of filamentous fungi spanning over 200 million years of evolution, and a comparative study with Aspergillus fumigatus and As pergillus oryzae, used in the production of sake, miso and soy sauce, provides new insight into eukaryotic genome evolution and gene regulation.
Abstract: The aspergilli comprise a diverse group of filamentous fungi spanning over 200 million years of evolution. Here we report the genome sequence of the model organism Aspergillus nidulans, and a comparative study with Aspergillus fumigatus, a serious human pathogen, and Aspergillus oryzae, used in the production of sake, miso and soy sauce. Our analysis of genome structure provided a quantitative evaluation of forces driving long-term eukaryotic genome evolution. It also led to an experimentally validated model of mating-type locus evolution, suggesting the potential for sexual reproduction in A. fumigatus and A. oryzae. Our analysis of sequence conservation revealed over 5,000 non-coding regions actively conserved across all three species. Within these regions, we identified potential functional elements including a previously uncharacterized TPP riboswitch and motifs suggesting regulation in filamentous fungi by Puf family genes. We further obtained comparative and experimental evidence indicating widespread translational regulation by upstream open reading frames. These results enhance our understanding of these widely studied fungi as well as provide new insight into eukaryotic genome evolution and gene regulation.
1,297 citations
DSM1, Delft University of Technology2, University of Nottingham3, Technical University of Denmark4, Wageningen University and Research Centre5, University of Sheffield6, Utrecht University7, Biomax Informatics AG8, CLC bio9, University of Liverpool10, Ghent University11, University of Manchester12, University of Provence13, University of Groningen14, Pasteur Institute15, University of Amsterdam16, University of Angers17, Leiden University18, Radboud University Nijmegen19, University of Szeged20
TL;DR: The filamentous fungus Aspergillus niger is widely exploited by the fermentation industry for the production of enzymes and organic acids, particularly citric acid, and the sequenced genome revealed a large number of major facilitator superfamily transporters and fungal zinc binuclear cluster transcription factors.
Abstract: The filamentous fungus Aspergillus niger is widely exploited by the fermentation industry for the production of enzymes and organic acids, particularly citric acid. We sequenced the 33.9-megabase genome of A. niger CBS 513.88, the ancestor of currently used enzyme production strains. A high level of synteny was observed with other aspergilli sequenced. Strong function predictions were made for 6,506 of the 14,165 open reading frames identified. A detailed description of the components of the protein secretion pathway was made and striking differences in the hydrolytic enzyme spectra of aspergilli were observed. A reconstructed metabolic network comprising 1,069 unique reactions illustrates the versatile metabolism of A. niger. Noteworthy is the large number of major facilitator superfamily transporters and fungal zinc binuclear cluster transcription factors, and the presence of putative gene clusters for fumonisin and ochratoxin A synthesis.
1,161 citations
National Institute of Advanced Industrial Science and Technology1, National Institute of Technology and Evaluation2, Intec, Inc.3, Tohoku University4, University of Tokyo5, Nagoya University6, Tokyo University of Agriculture and Technology7, University of Manchester8, Broad Institute9, George Washington University10, Agricultural Research Service11, University of Nottingham12, Tulane University13, J. Craig Venter Institute14, Kikkoman15, Kyushu University16, Nara Institute of Science and Technology17
TL;DR: Specific expansion of genes for secretory hydrolytic enzymes, amino acid metabolism and amino acid/sugar uptake transporters supports the idea that A. oryzae is an ideal microorganism for fermentation.
Abstract: The genome of Aspergillus oryzae, a fungus important for the production of traditional fermented foods and beverages in Japan, has been sequenced. The ability to secrete large amounts of proteins and the development of a transformation system have facilitated the use of A. oryzae in modern biotechnology. Although both A. oryzae and Aspergillus flavus belong to the section Flavi of the subgenus Circumdati of Aspergillus, A. oryzae, unlike A. flavus, does not produce aflatoxin, and its long history of use in the food industry has proved its safety. Here we show that the 37-megabase (Mb) genome of A. oryzae contains 12,074 genes and is expanded by 7-9 Mb in comparison with the genomes of Aspergillus nidulans and Aspergillus fumigatus. Comparison of the three aspergilli species revealed the presence of syntenic blocks and A. oryzae-specific blocks (lacking synteny with A. nidulans and A. fumigatus) in a mosaic manner throughout the genome of A. oryzae. The blocks of A. oryzae-specific sequence are enriched for genes involved in metabolism, particularly those for the synthesis of secondary metabolites. Specific expansion of genes for secretory hydrolytic enzymes, amino acid metabolism and amino acid/sugar uptake transporters supports the idea that A. oryzae is an ideal microorganism for fermentation.
1,149 citations