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This book provides a comprehensive examination of biochemical and genetic regulatory phenomena as they relate to the activity of actinomycete secondary metabolic pathways and the functioning of secondary metabolites as endogenous effectors of cytodifferentiation. Approximately 50 illustrations accompany the text.
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This book provides a comprehensive examination of biochemical and genetic regulatory phenomena as they relate to the activity of actinomycete secondary metabolic pathways and the functioning of secondary metabolites as endogenous effectors of cytodifferentiation. Approximately 50 illustrations accompany the text.
This book provides in-depth information about the ecology, diversity and applications of Actinomycetes. The book is divided into two major parts. The first part discusses the diversity, chemical biology and ecology of Actinomycetes. It also covers the discovery of natural products from soil, endophytic and marine-derived Actinomycetes. It includes natural product discovery, chemical biology, new methods for discovering secondary metabolites, structure elucidation and biosynthetic research of natural products. The chapters in this part focus on the effects of biological and chemical elicitation at molecular level on secondary metabolism in Actinomycetes. The second part of the book discusses genomic and synthetic biology approaches in Actinomycetes drug discovery. This part includes chapters focused on the application of metabolic engineering to optimize natural product synthesis and the use of omics data in engineering of regulatory genes. It covers the advanced tools of synthetic biology and metabolic engineering including cluster assembly, CRISPR/Cas9 technologies, and chassis strain development for natural product overproduction in Actinomycetes. It describes the use of bioinformatics tools for reprogramming of biosynthetic pathways through polyketide synthase and non-ribosomal peptide synthetase engineering. These advanced genomic and molecular tools are expected to accelerate the discovery and development of new natural products from Actinomycetes with medicinal and other industrial applications. The book is useful to researchers and students in the field of microbiology, pharmaceutical sciences and drug discovery.
Actinobacteria (Actinomycetes) represent one of the largest and most diverse phyla among Bacteria. The remarkable diversity is displayed by various lifestyles, distinct morphologies, a wide spectrum of physiological and metabolic activities, as well as genetics. Interestingly, most Actinobacteria have a high GC-content (ranging from 51% to >70%) and belong to Gram-positive or Gram-variable type microbes. Many species are well known for large genomes which may be of linear style as in case of rhodococci or circular. Many of those harbor linear megaplasmids as a kind of genetic storage device. Frequently gene redundancy is reported and in most cases the evolutionary history or a functional role remains enigmatic. Nevertheless these large genomes and megaplasmids provide access to a number of potential (homologous) biocatalysts which await elucidation. Actinobacteria are well known for their biotechnological potential which is exemplarily described for amino acid producing Corynebacteria, secondary metabolite producing Streptomyces, pathogenic targets as Nocardia and Mycobacteria, carotenoid building Micrococcus strains, acid fermenting Propionibacteria, health and food related Bifidobacterium strains, rubber degrading Gordonia species, and organic pollutant degrading rhodococci among others. In many cases individual pathways or enzymes can be modified or recombinantly employed for biocatalysis. Even some genetic tools to work directly in those microbes have been successfully used as for example in Corynebacterium or in Rhodococcus species. During the last decade more and more genomes have been sequenced and made available for data mining and become accessible by state of the art genomic manipulation methods as minimal genomes, knock-out or artificial evolution. With respect to this large and ancient phylum many questions can be asked either from a scientific or industrial point of view. In order to provide some crystallization points we like to raise some examples as follows. How small can be an actinobacterial genome? What is the driving force to comprise large and repetitive genomes/megaplasmids? What is needed to generate an actinobacterial power house for industry? Can we annotate novel biocatalysts from scratch and improve functional annotation? What are common and different features with respect to other bacteria and/or fungi? How many novel antibiotics are hidden among Actinobacteria? Is there more potential among extremophile members or are they only specialized? Here especially the production of natural compounds is of high interest.
Beyond being the most important natural compound source, actinomycetes are the origin of up to two-thirds of all clinically used antibiotics. Currently, new antimicrobials are urgently needed, as infections caused by antibiotic-resistant pathogens are on the rise. In the identification of new antibiotics, many scientists are currently investigating biosynthetic aspects of antibiotic production in actinomycetes. Since the emergence of next-generation sequencing technologies, the field of antibiotics research has experienced a remarkable revival. These bacteria have the potential to produce more antibiotics than previously thought possible. Some antibiotics are produced in standard media, while others require the presence of a specific signaling molecule in the medium. Others, however, are only produced when the native regulation of the biosynthesis gene cluster is overruled. This book covers topics in the field of antibiotic-producing actinomycetes. The following tops are addressed: - Approaches to access novel antibiotic producers for novel natural compounds - Omics and genome mining approaches for the discovery of novel natural compounds - Analyses and genetic engineering of antibiotic biosynthesis - Regulation of the secondary metabolism in actinomycetes
Based on available genome sequences and homology searches with already described systems of close relatives, the up to now mostly unknown repertoire of nitrogen metabolism-related genes in the genus Mycobacterium was discovered and putative pathways and regulatory networks have been constructed and compared. In respect to carbohydrate metabolism, the repertoire of carbohydrate uptake systems in the genus Mycobacterium was studied and predictions about the comparative growth potential of M. smegmatis and Mycobacterium tuberculosis on various carbon sources were provided. In a similar approach, the genome of the industrial relevant probiotic Bifidobacterium longum has been examined for carbohydrate uptake systems. Furthermore, the proteolytic potential of various Corynebacterium species based on all available genome sequences was compared and resulted in a more complete view on the housekeeping protease systems as well as on proteases putatively involved in pathogenicity and virulence of Corynebacterium diphtheriae.