Genome Mining Isolation And Characterization Of Novel Lasso Peptides And Their Utilization In Drug Development

Lasso peptides form a growing family of fascinating ribosomally-synthesized and post-translationally modified peptides produced by bacteria. They contain 15 to 24 residues and share a unique interlocked topology that involves an N-terminal 7 to 9-residue macrolactam ring where the C-terminal tail is threaded and irreversibly trapped. The ring results from the condensation of the N-terminal amino group with a side-chain carboxylate of a glutamate at position 8 or 9, or an aspartate at position 7, 8 or 9. The trapping of the tail involves bulky amino acids located in the tail below and above the ring and/or disulfide bridges connecting the ring and the tail. Lasso peptides are subdivided into three subtypes depending on the absence (class II) or presence of one (class III) or two (class I) disulfide bridges. The lasso topology results in highly compact structures that give to lasso peptides an extraordinary stability towards both protease degradation and denaturing conditions. Lasso peptides are generally receptor antagonists, enzyme inhibitors and/or antibacterial or antiviral (anti-HIV) agents. The lasso scaffold and the associated biological activities shown by lasso peptides on different key targets make them promising molecules with high therapeutic potential. Their application in drug design has been exemplified by the development of an integrin antagonist based on a lasso peptide scaffold. The biosynthesis machinery of lasso peptides is therefore of high biotechnological interest, especially since such highly compact and stable structures have to date revealed inaccessible by peptide synthesis. Lasso peptides are produced from a linear precursor LasA, which undergoes a maturation process involving several steps, in particular cleavage of the leader peptide and cyclization. The post-translational modifications are ensured by a dedicated enzymatic machinery, which is composed of an ATP-dependent cysteine protease (LasB) and a lactam synthetase (LasC) that form an enzymatic complex called lasso synthetase. Microcin J25, produced by Escherichia coli AY25, is the archetype of lasso peptides and the most extensively studied. To date only around forty lasso peptides have been isolated, but genome mining approaches have revealed that they are widely distributed among Proteobacteria and Actinobacteria, particularly in Streptomyces, making available a rich resource of novel lasso peptides and enzyme machineries towards lasso topologies.

Comprehensive Natural Products III, Third Edition, Seven Volume Set updates and complements the previous two editions, including recent advances in cofactor chemistry, structural diversity of natural products and secondary metabolites, enzymes and enzyme mechanisms and new bioinformatics tools. Natural products research is a dynamic discipline at the intersection of chemistry and biology concerned with isolation, identification, structure elucidation, and chemical characteristics of naturally occurring compounds such as pheromones, carbohydrates, nucleic acids and enzymes. This book reviews the accumulated efforts of chemical and biological research to understand living organisms and their distinctive effects on health and medicine and to stimulate new ideas among the established natural products community. Provides readers with an in-depth review of current natural products research and a critical insight into the future direction of the field Bridges the gap in knowledge by covering developments in the field since the second edition published in 2010 Split into 7 sections on key topics to allow students, researchers and professionals to find relevant information quickly and easily Ensures that the knowledge within is easily understood by and applicable to a large audience

Prof Upton is the director of Amprologix, a company developing new bacteriocins; the other editors declare no competing interest in regard to editing this Research Topic.

This book explores the role of in silico deployment in connection with modulation techniques for improving sustainability and competitiveness in the agri-food sector; pharmacokinetics and molecular docking studies of plant-derived natural compounds; and their potential anti-neurodegenerative activity. It also investigates biochemical pathways for bacterial metabolite synthesis, fungal diversity and plant-fungi interaction in plant diseases, methods for predicting disease-resistant candidate genes in plants, and genes-to-metabolites and metabolites-to-genes approaches for predicting biosynthetic pathways in microbes for natural product discovery. The respective chapters elaborate on the use of in situ methods to study biochemical pathways for bacterial metabolite synthesis; tools for plant metabolites in defence; plant secondary metabolites in defence; plant growth metabolites; characterisation of plant metabolites; and identification of plant derived metabolites in the context of plant defence. The book offers an unprecedented resource, highlighting state-of-the-art research work that will greatly benefit researchers and students alike, not only in the field of agriculture but also in many disciplines in the life sciences and plant sciences.

Radical SAM Enzymes, Volume 606, the latest release in the Methods in Enzymology series, highlights new advances in the field, with this new volume presenting interesting chapters on the Characterization of the glycyl radical enzyme choline trimethylamine-lyase and its radical S-adenosylmethionine activating enzyme, Diphathimide biosynthesis, Radical SAM glycyl radical activating enzymes, Radical SAM enzyme BioB in the biosynthesis of biotin, Biogenesis of the PQQ cofactor, Role of MoaAC in the biogenesis of the molybdenum cofactor, Biosynthesis of the nitrogenase cofactor, Bioinformatics of the radical SAM superfamily, The involvement of SAM radical enzymes in the biosynthesis of methanogenic coenzymes, methanopterin and coenzyme F420, and more. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in the Methods in Enzymology series Covers radical SAN enzymes in detail

Dr. Steven J. Fisher is a young and brilliant biochemist (special subject: the female orgasm). He's invented a Viagra-like pill for women—now he just needs his results to be perfect. Annie is an orgasmically-challenged arts student (special subject: Victorian semicolons). She's just volunteered to be one of Fisher's case studies—but for some reason his miracle treatment isn't working. As scientist and subject bond over romantic meals lit by the flickering glow of a Bunsen burner, Dr. Fisher is surprised to find his feelings taking a most unscientifc turn. . . What if love is one thing science can't explain?

Antimicrobial resistance will become a global health threat since antimicrobial treatments continue at the forefront of the defense against microbial infections. To respond to the issue, this detailed book explores vital methodologies currently in use to advance our understanding of antibiotic issues and answer the worldwide demand for novel antibiotics therapies. Beginning with a review chapter that guides the reader through the worldwide demand for novel antibiotics therapies, the volume continues with sections covering new screening procedures and environmental sources, advances in analytical, microbiological, and biotechnological methodologies, antibiotic production and antibiotic resistances, as well as considerations of drug trials and clinical concerns regarding multi-resistant patients. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Antimicrobial Therapies: Methods and Protocols provides a reference source for health, laboratory, and industrial professionals, as well as for graduate students in a number of bio-sanitary disciplines, including medicine, nursery, biotechnology, veterinary, microbiology, genetics, molecular biology, nutrition, farming, and more. Chapter “14” is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.