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1. Dysfunction of the heteromeric Kv7.3/Kv7.5 potassium channel is associated with autism spectrum disorders

Author

Mette eGilling, Hanne Borger Rasmussen, Kirstine eCalloe, Ana Filipa Sequeira, Marta eBaretto, Guiomar eOliveira, Joana eAlmeida, Marlene Briciet Lauritsen, Reinhard eUllmann, Susanne Eriksen Boonen, Karen eBrøndum-Nielsen, Vera M Kalscheuer, Zeynep eTümer, Astrid M. Vicente, Nicole eSchmitt, and Niels eTommerup

Subjects
autism, SNP, translocation, KCNQ3, KCNQ5, KV7.3, Genetics, QH426-470
Abstract

Heterozygous mutations in the KCNQ3 gene on chromosome 8q24 encoding the voltage-gated potassium channel KV7.3 subunit have previously been associated with rolandic epilepsy and idiopathic generalized epilepsy (IGE) including benign neonatal convulsions. We identified a de novo t(3;8)(q21;q24) translocation truncating KCNQ3 in a boy with childhood autism. In addition, we identified a c.1720C>T [p.P574S] nucleotide change in three unrelated individuals with childhood autism and no history of convulsions. This nucleotide change was previously reported in patients with rolandic epilepsy or IGE and has now been annotated as a very rare SNP (rs74582884) in dbSNP. The p.P574S Kv7.3 variant significantly reduced potassium current amplitude in Xenopus laevis oocytes when co-expressed with Kv7.5 but not with Kv7.2 or Kv7.4. The nucleotide change did not affect trafficking of heteromeric mutant Kv7.3/2, Kv7.3/4 or Kv7.3/5 channels in HEK 293 cells or primary rat hippocampal neurons. Our results suggest that dysfunction of the heteromeric Kv7.3/5 channel is implicated in the pathogenesis of some forms of autism spectrum disorders (ASD), epilepsy and possibly other psychiatric disorders and therefore, KCNQ3 and KCNQ5 are suggested as candidate genes for these disorders.

Published
2013
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4. A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder

Author

Veronica J. Vieland, Stephen W. Scherer, Alison K. Merikangas, Naisha Shah, Edwin H. Cook, William M. McMahon, Kirsty Wing, Sabata C. Lund, Jacob A. S. Vorstman, Judith Conroy, Sabine M. Klauck, John B. Vincent, Astrid M. Vicente, Carine Mantoulan, Barbara Parrini, Jeremy R. Parr, Herman van Engeland, Jane McGrath, Guiomar Oliveira, Jonathan Green, James S. Sutcliffe, Peter Szatmari, Ann Le Couteur, Katerina Papanikolaou, Joseph Piven, Andrew Pickles, Gillian Baird, Inês Sousa, Gerard D. Schellenberg, Catarina Correia, Bennett L. Leventhal, Helen McConachie, Joseph T. Glessner, Fritz Poustka, Alistair T. Pagnamenta, Marion Leboyer, Nuala Sykes, Elena Maestrini, Penny Farrar, Maïté Tauber, Suzanne Foley, Richard Holt, Lonnie Zwaigenbaum, David J. Posey, John Tsiantis, Alexander Kolevzon, Agatino Battaglia, Maretha de Jonge, Hilary Coon, Gillian Hughes, John R. Gilbert, Patrick Bolton, Louise Gallagher, Jeff Munson, Kathy White, Michael L. Cuccaro, Annemarie Poustka, Daniel H. Geschwind, Richard Delorme, Annette Estes, Christine M. Freitag, Jillian P. Casey, Joana Almeida, Dalila Pinto, Simon Wallace, Sean Brennan, Stephen J. Guter, Stanley F. Nelson, Michael Rutter, Ghazala Mirza, Anthony J. Bailey, Christina Corsello, Kerstin Wittemeyer, Christian R. Marshall, Janine A. Lamb, Catherine Lord, Hakon Hakonarson, Jiannis Ragoussis, Catalina Betancur, Geraldine Dawson, Eftichia Duketis, Sean Ennis, Fiorella Minopoli, Christopher Gillberg, Vera Stoppioni, Bridget A. Fernandez, Frederico Duque, Eric Fombonne, Ellen M. Wijsman, Bernadette Rogé, Vanessa Hus, Susan E. Folstein, Jonathan L. Haines, Denis C. Shields, Tiago R. Magalhaes, Andrew Green, Thomas Bourgeron, Brian L. Yaspan, Ann P. Thompson, Gudrun Nygren, Judith Miller, Susanne Thomson, Roberta Igliozzi, Ana Filipa Sequeira, Kai Wang, Brett S. Abrahams, John I. Nurnberger, Michael Gill, Thomas H. Wassink, Christopher J. McDougle, Marc N. Coutanche, Anthony P. Monaco, Nadia Bolshakova, Cecilia Kim, Raffaella Tancredi, Rita M. Cantor, Phil Cali, Fred R. Volkmar, Tom Berney, Margaret A. Pericak-Vance, Joachim Hallmayer, Joseph D. Buxbaum, Elena Bacchelli, Latha Soorya, Richard Anney, Regina Regan, University of Bologna, Open University of Israël, IRCCS Fondazione Stella Maris [Pisa], Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Goethe-University Frankfurt am Main, Memorial University of Newfoundland [St. John's], McGill University = Université McGill [Montréal, Canada], Johns Hopkins University (JHU), Autism Research Centre and Section of Developmental Psychiatry, University of Cambridge [UK] (CAM), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Psychiatrie génétique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Mondor de Recherche Biomédicale, The Hospital for sick children [Toronto] (SickKids), University of Toronto, Australian Resources Research Centre, Kensington, Sécurité et Qualité des Produits d'Origine Végétale (SQPOV), Avignon Université (AU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital des Enfants, CHU Toulouse [Toulouse], School of Chemistry, Dalhousie University [Halifax], DLR Institut für Planetenforschung, Deutsches Zentrum für Luft- und Raumfahrt [Berlin] (DLR), Department of Human Genetics, University of Chicago, University of Alberta, Génétique de l'autisme = Genetics of Autism (NPS-01), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), University of Koblenz-Landau, McMaster University [Hamilton, Ontario], The authors acknowledge the families participating in the study and the main funders of the Autism Genome Project Consortium (AGP): Autism Speaks (USA), the Health Research Board (HRB, Ireland), The Medical Research Council (MRC, UK), Genome Canada/Ontario Genomics Institute, and the Hilibrand Foundation (USA). Additional support for individual groups was provided by the US National Institutes of Health (NIH grants HD055751, HD055782, HD055784, HD35465, MH52708, MH55284, MH57881, MH061009, MH06359, MH066673, MH080647, MH081754, MH66766, NS026630, NS042165, NS049261), the Canadian Institute for Advanced Research (CIFAR), the Canadian Institutes for Health Research (CIHR), Assistance Publique–Hôpitaux de Paris (France), Autistica, Canada Foundation for Innovation/Ontario Innovation Trust, Deutsche Forschungsgemeinschaft (grant Po 255/17-4) (Germany), EC Sixth FP AUTISM MOLGEN, Fundação Calouste Gulbenkian (Portugal), Fondation de France, Fondation FondaMental (France), Fondation Orange (France), Fondation pour la Recherche Médicale (France), Fundação para a Ciência e Tecnologia (Portugal), the Hospital for Sick Children Foundation and University of Toronto (Canada), INSERM (France), Institut Pasteur (France), the Italian Ministry of Health (convention 181 of 19.10.2001), the John P. Hussman Foundation (USA), McLaughlin Centre (Canada), Ontario Ministry of Research and Innovation (Canada), the Seaver Foundation (USA), the Swedish Science Council, The Centre for Applied Genomics (Canada), the Utah Autism Foundation (USA) and the Wellcome Trust core award 075491/Z/04 (UK). We acknowledge support from the Autism Genetic Resource Exchange (AGRE) and Autism Speaks. We gratefully acknowledge the resources provided by the AGRE consortium and the participating AGRE families. AGRE is a program of Autism Speaks and is supported, in part, by grant 1U24MH081810 from the National Institute of Mental Health to Clara M. Lajonchere (PI). We wish to acknowledge the National Children’s Research Centre Our Lady’s Children’s Hospital Crumlin Ireland for providing additional support and the Wellcome Trust Case–Control Consortium for providing data sets that were used as part of this study. J.P.C is supported by an EMBARK postgraduate award from the Irish Research Council for Science, Engineering and Technology (IRCSET)., The AGRE Consortium, Casey JP, Magalhaes T, Conroy JM, Regan R, Shah N, Anney R, Shields DC, Abrahams BS, Almeida J, Bacchelli E, Bailey AJ, Baird G, Battaglia A, Berney T, Bolshakova N, Bolton PF, Bourgeron T, Brennan S, Cali P, Correia C, Corsello C, Coutanche M, Dawson G, de Jonge M, Delorme R, Duketis E, Duque F, Estes A, Farrar P, Fernandez BA, Folstein SE, Foley S, Fombonne E, Freitag CM, Gilbert J, Gillberg C, Glessner JT, Green J, Guter SJ, Hakonarson H, Holt R, Hughes G, Hus V, Igliozzi R, Kim C, Klauck SM, Kolevzon A, Lamb JA, Leboyer M, Le Couteur A, Leventhal BL, Lord C, Lund SC, Maestrini E, Mantoulan C, Marshall CR, McConachie H, McDougle CJ, McGrath J, McMahon WM, Merikangas A, Miller J, Minopoli F, Mirza GK, Munson J, Nelson SF, Nygren G, Oliveira G, Pagnamenta AT, Papanikolaou K, Parr JR, Parrini B, Pickles A, Pinto D, Piven J, Posey DJ, Poustka A, Poustka F, Ragoussis J, Roge B, Rutter ML, Sequeira AF, Soorya L, Sousa I, Sykes N, Stoppioni V, Tancredi R, Tauber M, Thompson AP, Thomson S, Tsiantis J, Van Engeland H, Vincent JB, Volkmar F, Vorstman JA, Wallace S, Wang K, Wassink TH, White K, Wing K, Wittemeyer K, Yaspan BL, Zwaigenbaum L, Betancur C, Buxbaum JD, Cantor RM, Cook EH, Coon H, Cuccaro ML, Geschwind DH, Haines JL, Hallmayer J, Monaco AP, Nurnberger JI Jr, Pericak-Vance MA, Schellenberg GD, Scherer SW, Sutcliffe JS, Szatmari P, Vieland VJ, Wijsman EM, Green A, Gill M, Gallagher L, Vicente A, Ennis S., McGill University, Institut National de la Recherche Agronomique (INRA)-Avignon Université (AU), Neuroscience Paris Seine (NPS), Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), University of Bologna/Università di Bologna, Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Memorial University of Newfoundland = Université Memorial de Terre-Neuve [St. John's, Canada] (MUN), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Candidate gene, Genome-wide association study, Linkage Disequilibrium, MESH: Child Development Disorders, Pervasive, Cohort Studies, MESH: Genotype, 0302 clinical medicine, MESH: Child, Cluster Analysis, Genetics(clinical), Copy-number variation, Child, MESH: Cohort Studies, Genetics (clinical), Original Investigation, SNPS, Genetics, 0303 health sciences, education.field_of_study, MESH: Middle Aged, MESH: Nuclear Family, MESH: Polymorphism, Single Nucleotide, Homozygote, MESH: Genetic Predisposition to Disease, Middle Aged, Autism spectrum disorder (ASD), 3. Good health, MESH: Linkage Disequilibrium, Female, MESH: DNA Copy Number Variations, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Homozygote, Adult, DNA Copy Number Variations, Genotype, Population, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Nuclear Family, 03 medical and health sciences, HOMOZYGOSITY MAPPING, mental disorders, medicine, Humans, Genetic Predisposition to Disease, ddc:610, AUTISM, GENOME-WIDE ASSOCIATION, education, 030304 developmental biology, MESH: Humans, Genetic heterogeneity, Haplotype, MESH: Adult, MESH: Haplotypes, medicine.disease, MESH: Cluster Analysis, MESH: Male, Haplotypes, Child Development Disorders, Pervasive, Perturbações do Desenvolvimento Infantil e Saúde Mental, MESH: Genome-Wide Association Study, Autism, MESH: Female, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data. Electronic supplementary material The online version of this article (doi:10.1007/s00439-011-1094-6) contains supplementary material, which is available to authorized users.

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5. Gene design, fusion technology and TEV cleavage conditions influence the purification of oxidized disulphide-rich venom peptides in Escherichia coli

Author

Luis Telo da Gama, Jeremy Turchetto, Carlos M. G. A. Fontes, Yoan Duhoo, Natalie J. Saez, Ana Filipa Sequeira, Marilyne Blémont, Nicolas Gilles, Fanny Peysson, Laurie Ramond, Catarina I. P. D. Guerreiro, Renaud Vincentelli, Vânia O. Fernandes, Hervé Darbon, Luís M. A. Ferreira, Universidade de Lisboa (ULISBOA), Architecture et fonction des macromolécules biologiques (AFMB), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), University of Madeira [Funchal], Département d'Ingénierie et d'Etudes des Protéines, CEN/Saclay, Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), Universidade de Lisboa ( ULISBOA ), Architecture et fonction des macromolécules biologiques ( AFMB ), Centre National de la Recherche Scientifique ( CNRS ) -Aix Marseille Université ( AMU ) -Institut National de la Recherche Agronomique ( INRA ), and Universidade de Lisboa = University of Lisbon (ULISBOA)

Subjects
0301 basic medicine, MESH: Oxidation-Reduction, MESH : Escherichia coli, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, medicine.medical_treatment, Escherichia coli (E. coli), Venom, medicine.disease_cause, Venom peptides, Applied Microbiology and Biotechnology, law.invention, MESH: Venoms, law, MESH: Genetic Vectors, High-throughput expression, TEV protease, MESH: Animals, Disulfides, Cloning, Molecular, MESH: Endopeptidases, MESH : Peptides, MESH: Escherichia coli, MESH: Peptides, MESH: Periplasm, Gene design, MESH : Endopeptidases, MESH : Genetic Vectors, Disulphide-rich peptides, Biochemistry, Periplasm, Recombinant DNA, MESH: Biotechnology, MESH: Peptide Biosynthesis, MESH : Periplasm, Oxidation-Reduction, Fusion protein, Biotechnology, Peptide Biosynthesis, MESH: High-Throughput Screening Assays, MESH : Recombinant Fusion Proteins, MESH : Cloning, Molecular, Recombinant Fusion Proteins, Genetic Vectors, Bioengineering, Biology, MESH : High-Throughput Screening Assays, MESH : Biotechnology, 03 medical and health sciences, Recombinant expression, Endopeptidases, Escherichia coli, medicine, MESH: Recombinant Fusion Proteins, Animals, MESH: Disulfides, MESH: Cloning, Molecular, MESH : Oxidation-Reduction, Protease, Venoms, Research, MESH : Solubility, [ SDV.BIO ] Life Sciences [q-bio]/Biotechnology, Periplasmic space, Molecular biology, High-Throughput Screening Assays, MESH: Solubility, 030104 developmental biology, Solubility, MESH : Venoms, MESH : Animals, MESH : Disulfides, Peptides, MESH : Peptide Biosynthesis, Cysteine
Abstract

Background Animal venoms are large, complex libraries of bioactive, disulphide-rich peptides. These peptides, and their novel biological activities, are of increasing pharmacological and therapeutic importance. However, recombinant expression of venom peptides in Escherichia coli remains difficult due to the significant number of cysteine residues requiring effective post-translational processing. There is also an urgent need to develop high-throughput recombinant protocols applicable to the production of reticulated peptides to enable efficient screening of their drug potential. Here, a comprehensive study was developed to investigate how synthetic gene design, choice of fusion tag, compartment of expression, tag removal conditions and protease recognition site affect levels of solubility of oxidized venom peptides produced in E. coli. Results The data revealed that expression of venom peptides imposes significant pressure on cysteine codon selection. DsbC was the best fusion tag for venom peptide expression, in particular when the fusion was directed to the bacterial periplasm. While the redox activity of DsbC was not essential to maximize expression of recombinant fusion proteins, redox activity did lead to higher levels of correctly folded target peptides. With the exception of proline, the canonical TEV protease recognition site tolerated all other residues at its C-terminus, confirming that no non-native residues, which might affect activity, need to be incorporated at the N-terminus of recombinant peptides for tag removal. Conclusions This study reveals that E. coli is a convenient heterologous host for the expression of soluble and functional venom peptides. Using the optimal construct design, a large and diverse range of animal venom peptides were produced in the µM scale. These results open up new possibilities for the high-throughput production of recombinant disulphide-rich peptides in E. coli. Electronic supplementary material The online version of this article (doi:10.1186/s12934-016-0618-0) contains supplementary material, which is available to authorized users.

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