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      Safety of the fungal workhorses of industrial biotechnology: update on the mycotoxin and secondary metabolite potential of Aspergillus niger, Aspergillus oryzae, and Trichoderma reesei

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          Abstract

          This review presents an update on the current knowledge of the secondary metabolite potential of the major fungal species used in industrial biotechnology, i.e., Aspergillus niger, Aspergillus oryzae, and Trichoderma reesei. These species have a long history of safe use for enzyme production. Like most microorganisms that exist in a challenging environment in nature, these fungi can produce a large variety and number of secondary metabolites. Many of these compounds present several properties that make them attractive for different industrial and medical applications. A description of all known secondary metabolites produced by these species is presented here. Mycotoxins are a very limited group of secondary metabolites that can be produced by fungi and that pose health hazards in humans and other vertebrates when ingested in small amounts. Some mycotoxins are species-specific. Here, we present scientific basis for (1) the definition of mycotoxins including an update on their toxicity and (2) the clarity on misclassification of species and their mycotoxin potential reported in literature, e.g., A. oryzae has been wrongly reported as an aflatoxin producer, due to misclassification of Aspergillus flavus strains. It is therefore of paramount importance to accurately describe the mycotoxins that can potentially be produced by a fungal species that is to be used as a production organism and to ensure that production strains are not capable of producing mycotoxins during enzyme production. This review is intended as a reference paper for authorities, companies, and researchers dealing with secondary metabolite assessment, risk evaluation for food or feed enzyme production, or considerations on the use of these species as production hosts.

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          antiSMASH 4.0—improvements in chemistry prediction and gene cluster boundary identification

          Abstract Many antibiotics, chemotherapeutics, crop protection agents and food preservatives originate from molecules produced by bacteria, fungi or plants. In recent years, genome mining methodologies have been widely adopted to identify and characterize the biosynthetic gene clusters encoding the production of such compounds. Since 2011, the ‘antibiotics and secondary metabolite analysis shell—antiSMASH’ has assisted researchers in efficiently performing this, both as a web server and a standalone tool. Here, we present the thoroughly updated antiSMASH version 4, which adds several novel features, including prediction of gene cluster boundaries using the ClusterFinder method or the newly integrated CASSIS algorithm, improved substrate specificity prediction for non-ribosomal peptide synthetase adenylation domains based on the new SANDPUMA algorithm, improved predictions for terpene and ribosomally synthesized and post-translationally modified peptides cluster products, reporting of sequence similarity to proteins encoded in experimentally characterized gene clusters on a per-protein basis and a domain-level alignment tool for comparative analysis of trans-AT polyketide synthase assembly line architectures. Additionally, several usability features have been updated and improved. Together, these improvements make antiSMASH up-to-date with the latest developments in natural product research and will further facilitate computational genome mining for the discovery of novel bioactive molecules.
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            Genome sequencing and analysis of the biomass-degrading fungus Trichoderma reesei (syn. Hypocrea jecorina).

            Trichoderma reesei is the main industrial source of cellulases and hemicellulases used to depolymerize biomass to simple sugars that are converted to chemical intermediates and biofuels, such as ethanol. We assembled 89 scaffolds (sets of ordered and oriented contigs) to generate 34 Mbp of nearly contiguous T. reesei genome sequence comprising 9,129 predicted gene models. Unexpectedly, considering the industrial utility and effectiveness of the carbohydrate-active enzymes of T. reesei, its genome encodes fewer cellulases and hemicellulases than any other sequenced fungus able to hydrolyze plant cell wall polysaccharides. Many T. reesei genes encoding carbohydrate-active enzymes are distributed nonrandomly in clusters that lie between regions of synteny with other Sordariomycetes. Numerous genes encoding biosynthetic pathways for secondary metabolites may promote survival of T. reesei in its competitive soil habitat, but genome analysis provided little mechanistic insight into its extraordinary capacity for protein secretion. Our analysis, coupled with the genome sequence data, provides a roadmap for constructing enhanced T. reesei strains for industrial applications such as biofuel production.
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              Bypassing Cultivation To Identify Bacterial Species

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                Author and article information

                Contributors
                jcf@bio.dtu.dk
                Journal
                Appl Microbiol Biotechnol
                Appl. Microbiol. Biotechnol
                Applied Microbiology and Biotechnology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0175-7598
                1432-0614
                6 October 2018
                6 October 2018
                2018
                : 102
                : 22
                : 9481-9515
                Affiliations
                [1 ]ISNI 0000 0001 2181 8870, GRID grid.5170.3, Department of Biotechnology and Biomedicine (DTU Bioengineering), , Technical University of Denmark, ; Søltofts Plads, B. 221, 2800 Kongens Lyngby, Denmark
                [2 ]ISNI 0000 0004 0373 0797, GRID grid.10582.3e, Department of Product Safety, , Novozymes A/S, ; Krogshoejvej 36, 2880 Bagsvaerd, Denmark
                [3 ]ISNI 0000 0004 0412 7324, GRID grid.422756.0, Department of Genomics and Bioinformatics, , Novozymes Inc., ; 1445 Drew Ave., Davis, CA 95618 USA
                [4 ]ISNI 0000 0004 0373 0797, GRID grid.10582.3e, Department of Fungal Strain Technology and Strain Approval Support, , Novozymes A/S, ; Krogshoejvej 36, 2880 Bagsvaerd, Denmark
                Author information
                http://orcid.org/0000-0002-0573-4340
                Article
                9354
                10.1007/s00253-018-9354-1
                6208954
                30293194
                20a9bb68-1153-4f3c-80fc-7dd447139ec7
                © The Author(s) 2018

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 12 July 2018
                : 28 August 2018
                : 29 August 2018
                Categories
                Mini-Review
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2018

                Biotechnology
                safety,mycotoxins,secondary metabolites,industrial enzymes
                Biotechnology
                safety, mycotoxins, secondary metabolites, industrial enzymes

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