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- Borodina, I., et al.
(author)
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Metabolic engineering of streptomyces
- 2009
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In: The Metabolic Pathway Engineering Handbook: Fundamentals. - 9781439802977 ; , s. 24-1-24-30
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Book chapter (other academic/artistic)abstract
- Some of the common soil microorganisms are actinomycetes, Gram-positive bacteria with high GC content. Because of their mycelial habit they were initially believed to be fungi, which reected in their name (mucus (lat.) means fungus). In 1939, one year before rediscovery of penicillin by Florey and Chain, soil microbiologist Waksman has set his lab on a quest for new antimicrobial drugs. From the previous studies he knew that actinomycetes can inhibit the growth of other soil bacteria through secretion of bioactive compounds, which he named “antibiotics” (anti (lat.) against, bio (lat.) life). Systematic search for antibiotics produced by actinomycetes resulted in the discovery of actinomycin (1940), clavacin, and streptothricin (1942), all of them sadly turned out to be toxic in animal tests. In 1943 Waksman’s student Schatz isolated streptomycin-producing strain of Streptomyces griseus.1 Streptomycin was not particularly toxic to animals and humans, but remarkably was the rst compound active against tuberculosis bacteria. Many pharmaceutical companies and research laboratories started to collect soil samples from all over the world in search of antibiotics-producing organisms. Most of the discoveries were made in the rst ten years of the “hunt,” the larger part involved Streptomyces species. Streptomyces is a genus in the genera of actinomycetes, many of these bacteria produce volatile compounds that give the earth its characteristic odor. Streptomyces proved to be an excellent source of secondary metabolites, including antibiotics, anticancerous agents, antihelmintic drugs, and other useful compounds (Table 24.1). At present more than half of antibiotics in clinical use are produced in Streptomyces species.
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| 4. |
- Patil, K. R., et al.
(author)
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Structure and flux analysis of metabolic networks
- 2009
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In: The Metabolic Pathway Engineering Handbook: Fundamentals. - 9781439802977 ; , s. 17 1-17 18
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Book chapter (other academic/artistic)abstract
- Conceptual understanding of complex cellular organization can be facilitated through a perspective based on the central dogma of biology1 (Figure 17.1). Accordingly, information coded in a genome is translated into proteins via mRNA. Proteins play a variety of roles in a cell, including that of enzymes, which selectively catalyze chemical transformation between metabolites. Ensemble of all nongenetically encoded compounds (thus, excluding mRNA, proteins, etc.) and enzymes operating on them is generally referred to as a metabolic network.2 In essence, metabolic networks convert nutrients available from environment into fundamental building blocks for the synthesis of proteins, DNA, and other cellular components. By providing energy and building blocks for growth and maintenance of cells, metabolic networks play a central role in sustaining life. is key role of metabolic networks in cellular operations is evident by two facts. Firstly, the basic architecture of metabolic networks is largely conserved across several dierent species ranging from microscopic bacteria to humans.3 Second, cellular response and adaptation to genetic/environmental perturbations is oen mediated through or reected in the operation of metabolic networks.4 Although the structure of metabolic networks dier signicantly at local levels (e.g., specic pathway structures),3,5 their large-scale conservancy across dierent species implies common biochemical and evolutionary principles underlying their operation.6,7 Understanding such general principles has great implications for: (i) correlating and extrapolating knowledge across dierent species, especially from model organisms (such as yeast) to humans, (ii) devising rational strategies for metabolic engineering, iii) nding remedies for metabolism related diseases, and (iv) synthetic biology.
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