Microbial Cell Factories Engineering for Production of Biomolecules presents a compilation of chapters written by eminent scientists worldwide. Sections cover major tools and technologies for DNA synthesis, design of biosynthetic pathways, synthetic biology tools, biosensors, cell-free systems, computer-aided design, OMICS tools, CRISPR/Cas systems, and many more. Although it is not easy to find relevant information collated in a single volume, the book covers the production of a wide range of biomolecules from several MCFs, including Escherichia coli, Bacillus subtilis, Pseudomonas putida, Streptomyces, Corynebacterium, Cyanobacteria, Saccharomyces cerevisiae, Pichia pastoris and Yarrowia lipolytica, and algae, among many others. This will be an excellent platform from which scientific knowledge can grow and widen in MCF engineering research for the production of biomolecules. Needless to say, the book is a valuable source of information not only for researchers designing cell factories, but also for students, metabolic engineers, synthetic biologists, genome engineers, industrialists, stakeholders and policymakers interested in harnessing the potential of MCFs in several fields. - Offers basic understanding and a clear picture of various MCFs - Explains several tools and technologies, including DNA synthesis, synthetic biology tools, genome editing, biosensors, computer-aided design, and OMICS tools, among others - Harnesses the potential of engineered MCFs to produce a wide range of biomolecules for industrial, therapeutic, pharmaceutical, nutraceutical and biotechnological applications - Highlights the advances, challenges, and future opportunities in designing MCFs

Plant gene transfer achieved in the early ‘80s paved the way for the exploitation of the potential of gene engineering to add novel agronomic traits and/or to design plants as factories for high added value molecules. For this latter area of research, the term "Molecular Farming" was coined in reference to agricultural applications in that major crops like maize and tobacco were originally used basically for pharma applications. The concept of the “green biofactory” implies different advantages over the typical cell factories based on animal cell or microbial cultures already when considering the investment and managing costs of fermenters. Although yield, stability, and quality of the molecules may vary among different heterologous systems and plants are competitive on a case-to-case basis, still the “plant factory” attracts scientists and technologists for the challenging features of low production cost, product safety and easy scale up. Once engineered, a plant is among the cheapest and easiest eukaryotic system to be bred with simple know-how, using nutrients, water and light. Molecules that are currently being produced in plants vary from industrial and pharmaceutical proteins, including medical diagnostics proteins and vaccine antigens, to nutritional supplements such as vitamins, carbohydrates and biopolymers. Convergence among disciplines as distant as plant physiology and pharmacology and, more recently, as omic sciences, bioinformatics and nanotechnology, increases the options of research on the plant cell factory. “Farming for Pharming” biologics and small-molecule medicines is a challenging area of plant biotechnology that may break the limits of current standard production technologies. The recent success on Ebola fighting with plant-made antibodies put a spotlight on the enormous potential of next generation herbal medicines made especially in the name of the guiding principle of reduction of costs, hence reduction of disparities of health rights and as a tool to guarantee adequate health protection in developing countries.

On July 30-31, 2018, the National Academies of Sciences, Engineering, and Medicine held a workshop titled Continuous Manufacturing for the Modernization of Pharmaceutical Production. This workshop discussed the business and regulatory concerns associated with adopting continuous manufacturing techniques to produce biologics such as enzymes, monoclonal antibodies, and vaccines. The participants also discussed specific challenges for integration across the manufacturing system, including upstream and downstream processes, analytical techniques, and drug product development. The workshop addressed these challenges broadly across the biologics domain but focused particularly on drug categories of greatest FDA and industrial interest such as monoclonal antibodies and vaccines. This publication summarizes the presentations and discussions from the workshop.

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.

To explore the role of the National Institutes of Health (NIH) in innovative drug development and its impact on patient access, the Board on Health Care Services and the Board on Health Sciences Policy of the National Academies jointly hosted a public workshop on July 24â€"25, 2019, in Washington, DC. Workshop speakers and participants discussed the ways in which federal investments in biomedical research are translated into innovative therapies and considered approaches to ensure that the public has affordable access to the resulting new drugs. This publication summarizes the presentations and discussions from the workshop.