Erythromycin, drug synthesized by the soil bacterium Streptomyces erythraeus and used in the treatment of throat infections, pneumonia, and other diseases. Erythromycin, an antibiotic that inhibits the synthesis of vital proteins in susceptible bacteria, may be either bacteriostatic (i.e., inhibiting bacterial reproduction but not killing bacterial cells) or bactericidal (i.e., killing bacteria by direct action), depending on its concentration and the type of microorganism against which it is used. Among the disease-causing agents susceptible to erythromycin are Staphylococcus aureus, several species of Streptococcus, Mycoplasma species, Legionella pneumophila (the bacterium that causes Legionnaire disease), and Corynebacterium diphtheriae (the causative agent of diphtheria) .
3. (a) Most antibiotics, or their precursors, are obtained from microorganisms that have been bred to...
(b) One method of obtaining novel variants of erythromycin is to introduce mutations into the PKS genes and thereby remove the enzyme activity associated with a given domain. By writing down the transformations catalysed by each domain of DEBS1 and DEBS2, select which of the following four novel erythromycin derivatives (8-11) would be obtained if the first enoylreductase domain (ER) in DEBS2 were rendered inactive by mutation. Curly-arrow mechanisms for each step are not required. (4 points) Hoʻ =o HO...
(c) Briefly explain how erythromycin-producing bacteria (Streptomyces) avoid being killed by the antibiotic, and hence outline a potential problem associated with efforts to obtain novel erythromycin analogues by re-engineering the native gene cluster for erythromycin biosynthesis. (3 points)
(b) One method of obtaining novel variants of erythromycin is to introduce mutations into the PKS genes and thereby remove the enzyme activity associated with a given domain. By writing down the transformations catalysed by each domain of DEBS1 and DEBS2, select which of the following four novel erythromycin derivatives (8-11) would be obtained if the first enoylreductase domain (ER) in DEBS2 were rendered inactive by mutation. Curly-arrow mechanisms for each step are not required. (4 points)