Erythromycin genetic engineering

In some cases enzymes can increase the rate of reaction by up to lO times. Carnell and Roberts (1997) have briefly discussed the scope of biotransformations that are used to make pharmaceuticals like penicillins, cephalosporines, erythromycin, lovastatin, cyclosporin, etc., and for food additives like citric acid, L-glutamate, and L-lysine. A very successful transformation by Zeneca has been that of benzene reduction, with Pseudomonase Putida, to dihydrocatechol and catechol the dihydro derivative is used to produce (+/-) pinitol. Fluorobenzene has been converted to fluorodihydrocatechol, an intermediate for pharmaceuticals. The highly stereo selective Bayer-Villeger reaction has been carried out with genetically engineered S-cerevisvae. Hydrolases have allowed enantioselective, and in some cases regioselective, hydrolysis of racemic esters. 

Figure 11.4 6-DEBS 1, 2 and 3 that are modularly organized PKSs direct the biosynthesis of erythromycin A (a), and genetic engineering on genes encoding DEBSs gave rise to various 6-DEB analogs (b)...

Keywords Aliphatic polyketides Biosynthesis Polyketide Synthase Genetic Engineering Erythromycin A Rapamycin. 

Alternatively, if the producer of the natural compound is a microorgaiusm, fermentation is usually the method of choice. Today, many important pharmaceuticals are isolated from fermentation broths, including the immunosuppressives cyclosporin A, tacrolimus (FK-506), and sirolimns (rapamycin) the antibiotics erythromycin and vancomycin and human insnlin. By genetic engineering, microorganisms can be optimized for the production of one single compound, and this can result in an increased product titer and a facilitated isolation procedure. Subsection 5.3.1 to Subsection 5.3.4 will focus on the production of natural product scaffolds by fermentation of microorganisms. 

Mato JM, Alvarez L, Ortiz P, Pajares MA (1997) S-adenosylmethionine synthesis molecular mechanisms and clinical implications. Pharmacol Ther 73 265-280 Matos JR, Raushel EM, Wong CH (1987) S-Adenosylmethionine study on chemical and enzymatic synthesis. Biotechnol Appl Biochem 9 39-52 Minas W, Brunker P, Kallio PT, Bailey JE (1998) Improved erythromycin production in a genetically engineered industrial strain of Saccharopolyspora erythraea. Biotechnol Prog 14 561-566... 

A genetically-engineered strain of Saccharopolyspora erythraea has been used to produce 2-nor-erythromycins. A mutant strain of S. fradiae generates tylosin analogues in which the mycinose sugar unit is converted to 2-demethoxy, 2-demethoxy-4-epi, and 2-0-demethyl derivatives. 4 -0-(4-methoxyphenyl)-acetyl-tylosin has... 

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