Showing papers by "Arnold L. Demain published in 2017"

The antibiotic resistance crisis, with a focus on the United States

Abstract: Beginning with the discovery of penicillin by Alexander Fleming in the late 1920s, antibiotics have revolutionized the field of medicine. They have saved millions of lives each year, alleviated pain and suffering, and have even been used prophylactically for the prevention of infectious diseases. However, we have now reached a crisis where many antibiotics are no longer effective against even the simplest infections. Such infections often result in an increased number of hospitalizations, more treatment failures and the persistence of drug-resistant pathogens. Of particular concern are organisms such as methicillin-resistant Staphylococcus aureus, Clostridium difficile, multidrug and extensively drug-resistant Mycobacterium tuberculosis, Neisseria gonorrhoeae, carbapenem-resistant Enterobacteriaceae and bacteria that produce extended spectrum β-lactamases, such as Escherichia coli. To make matters worse, there has been a steady decline in the discovery of new and effective antibiotics for a number of reasons. These include increased costs, lack of adequate support from the government, poor returns on investment, regulatory hurdles and pharmaceutical companies that have simply abandoned the antibacterial arena. Instead, many have chosen to focus on developing drugs that will be used on a chronic basis, which will offer a greater profit and more return on investment. Therefore, there is now an urgent need to develop new and useful antibiotics to avoid returning to the 'pre-antibiotic era'. Some potential opportunities for antibiotic discovery include better economic incentives, genome mining, rational metabolic engineering, combinatorial biosynthesis and further exploration of the earth's biodiversity.

Production of valuable compounds by molds and yeasts.

Abstract: We are pleased to dedicate this paper to Dr Julian E Davies. Julian is a giant among microbial biochemists. He began his professional career as an organic chemistry PhD student at Nottingham University, moved on to a postdoctoral fellowship at Columbia University, then became a lecturer at the University of Manchester, followed by a fellowship in microbial biochemistry at Harvard Medical School. In 1965, he studied genetics at the Pasteur Institute, and 2 years later joined the University of Wisconsin in the Department of Biochemistry. He later became part of Biogen as Research Director and then President. After Biogen, Julian became Chair of the Department of Microbiology at the University of British Columbia in Vancouver, Canada, where he has contributed in a major way to the reputation of this department for many years. He also served as an Adjunct Professor at the University of Geneva. Among Julian's areas of study and accomplishment are fungal toxins including α-sarcin, chemical synthesis of triterpenes, mode of action of streptomycin and other aminoglycoside antibiotics, biochemical mechanisms of antibiotic resistance in clinical isolates of bacteria harboring resistance plasmids, their origins and evolution, secondary metabolism of microorganisms, structure and function of bacterial ribosomes, antibiotic resistance mutations in yeast ribosomes, cloning of resistance genes from an antibiotic-producing microbe, gene cloning for industrial purposes, engineering of herbicide resistance in useful crops, bleomycin-resistance gene in clinical isolates of Staphylococcus aureus and many other topics. He has been an excellent teacher, lecturing in both English and French around the world, and has organized international courses. Julian has also served on the NIH study sections, as Editor for several international journals, and was one of the founders of the journal Plasmid. We expect the impact of Julian's accomplishments to continue into the future.

Useful Microbial Enzymes—An Introduction

Abstract: Enzymes are important due to their many useful properties. Their development, to a great extent, has been possible due to the availability of microbial sources. Microorganisms are of much attention because they can be produced economically and are amenable to genetic improvement. Microbial enzymes have replaced many plant and animal enzymes. They have found application in many industries including foods, beverages, pharmaceuticals, detergents, textiles, leather, chemicals, biofuels, animal feed, personal care, pulp and paper, diagnostics, and therapy. New molecular methods, including genomics and metagenomics, are being employed for the discovery of new enzymes from microbes. The development of recombinant DNA technology has had a major effect on production levels of enzymes and represent a way to overproduce industrially important microbial, plant, and animal enzymes. It has been estimated that between 50–60% of the world enzyme market is supplied by recombinant enzymes. In addition, directed evolution techniques have allowed design of enzyme specificities and better performance.

An Overview of the Industrial Aspects of Antibiotic Discovery

Abstract: Microorganisms have provided an essential role in the production of natural products, such as antibiotics. Antibiotics are often produced as secondary metabolites, compounds not required for the normal growth and development of the organism. However, they may also be either semisynthetically produced from natural products or chemically synthesized based on the structure of the natural products. Beginning with Alexander Fleming’s discovery of penicillin in 1928, the field of medicine has seen a breakthrough in the different types of antibiotics available to treat bacterial infections. These include β-lactams (penicillins and cephalosporins), tetracyclines, aminoglycosides, chloramphenicol, macrolides, quinolones, and glycopeptides. For over half a century, antibiotics have saved millions of lives, eradicated disease, reduced pain and suffering, and even drastically increased the human life expectancy. Unfortunately, we have seen a decline in the discovery of new and effective antibiotics over the last few decades. Pharmaceutical companies are facing a number of challenges, such as short treatment durations, increased cost of clinical trials, brief window before the products become generics, and the growing problem of antibiotic resistance. Many of the major pharmaceutical companies have abandoned the antibiotic field, leaving much of the discovery efforts to small companies, new companies, and the biotechnology industry. Despite these challenges, other promising opportunities exist for the discovery of new drugs, such as high-throughput screening of natural product libraries, combinatorial chemistry of natural product scaffolds, genomics, proteomics, metabolomics, and discoveries in biodiversity, genome mining, and systems biology. Furthermore, we must also focus our efforts on the vast majority of microorganisms existing in nature that have yet to be cultured in the laboratory, for they too will likely provide us with a rich source of antimicrobials.

Bioactive Products from Fungi

Abstract: Fungi are amazing producers of natural products. They are crucial to the health and the well-being of people throughout the world. They are excellent producers of hydrolytic enzymes, biofuels, organic acids, polysaccharides, and secondary metabolites such as antibiotics, anticancer drugs, hypocholesterolemic agents, immunosuppressants, and others. This chapter centers on these fungal products, especially valuable secondary metabolites, the discovery of which goes back eighty-seven years when penicillin was discovered by Alexander Fleming.

Nutritional control of antibiotic production by Streptomyces platensis MA7327: importance of l -aspartic acid

Abstract: Streptomyces platensis MA7327 is a bacterium producing interesting antibiotics, which act by the novel mechanism of inhibiting fatty acid biosynthesis. The antibiotics produced by this actinomycete are platensimycin and platencin plus some minor related antibiotics. Platensimycin and platencin have activity against antibiotic-resistant bacteria such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus; they also lack toxicity in animal models. Platensimycin also has activity against diabetes in a mouse model. We have been interested in studying the effects of primary metabolites on production of these antibiotics in our chemically defined production medium. In the present work, we tested 32 primary metabolites for their effect. They included 20 amino acids, 7 vitamins and 5 nucleic acid derivatives. Of these, only l-aspartic acid showed stimulation of antibiotic production. We conclude that the stimulatory effect of aspartic acid is due to its role as a precursor involved in the biosynthesis of aspartate-4-semialdehyde, which is the starting point for the biosynthesis of the 3-amino-2,4-dihydroxy benzoic acid portion of the platensimycin molecule.

Enzymes of industrial interest

Abstract: Durante much os anos, las enzimas industriales han jugado un papel importante en el beneficio de nuestra sociedad debido a sus muchas propiedades utiles y una amplia gama de aplicaciones. Son elementos clave en el progreso de muchas industrias incluyendo alimentos, beb idas, productos farmaceuticos, diagnostico, terapia, cuidado personal, alimento para ganado , detergentes, pulpa y papel, textiles, cuero, productos quimicos y biocombustibles. Durante las ultimas decadas, las enzimas microbianas han reemplazado muchas enzi mas vegetales y animales. Esto se debe a que las enzimas microbianas estan ampliamente disponibles y se producen economicamente en fermentaciones cortas y medios de cultivo economicos. La deteccion es simple, y la mejora de la s cepas para aumentar la produ ccion ha sido muy exitosa. Los avances en la tecnologia del ADN recombinante han tenido un efecto importante en los niveles de produccion de enzimas y representan una forma de sobreproducir enzimas microbianas, vegetales y animales industrialmente importan tes. Se ha calculado que el 50 - 60% del mercado mundial de enzimas es suministra do con enzimas recombinantes. Metodos moleculares, in cluyendo genomica y metagenomica , han sido utilizados para el descubrimiento de nuevas enzimas de microbios. Ademas, la evolucion dirigida ha permitido el diseno de especificidades enzimaticas y un mejor rendimiento