Yield Of Erythromycin Research Articles

Saccharopolyspora erythraea-catalyzed bioconversion of 6-deoxyerythronolide B analogs for production of novel erythromycins

A method was developed for the large-scale bioconversion of novel 6-deoxyerythronolide B (6-dEB) analogs into erythromycin analogs. Erythromycin biosynthesis in Saccharopolyspora erythraea proceeds via the formation of a polyketide aglycone, 6-dEB, which is subsequently glycosylated, hydroxylated and methylated to yield the antibiotic erythromycin A. A modular polyketide synthase (PKS) directs 6-dEB synthesis using a dedicated set of active sites for the condensation of each of seven propionate units. Strategies based on genetic manipulation and precursor feeding are available for the efficient generation of novel 6-dEB analogs using a plasmid-based system in Streptomyces coelicolor. 6-dEB and 13-substituted 6-dEB analogs produced in this manner were fed to S. erythraea mutants which could not produce 6-dEB, yet retained their 6-dEB modification systems, and resulted in the generation of erythromycin A and 13-substituted erythromycin A analogs. Erythromycin B, C and D analogs were observed as intermediates of the process. Dissolved oxygen, temperature, the specific aglycone feed concentration, and pH were found to be important for obtaining a high yield of erythromycin A analogs. Cultivation conditions were identified which resulted in the efficient bioconversion of 6-dEB analogs into erythromycin A analogs, which this process demonstrated at the 100 l scale.

Extraction of erythromycin from fermentation broth using salt-induced phase separation processes

Abstract Extraction of erythromycin from fermentation broth using salt-induced phase separation processes has been examined. In this process, the fermentation broth was first mixed with organic solvent acetonitrile to form a homogeneous mixture. Then the mixture was separated into two phases by adding an inorganic salt, such as NaCl, Na2SO4. Accompanying phase separation, erythromycin was extracted from broth to organic phase. Erythromycin was recovered finally from solvents by vacuum distillation and crystallization. The phase equilibrium of water–acetonitrile systems was determined at different salt concentrations. The extraction yield and partition coefficients of erythromycin were measured at different operative conditions. It was found that comparing with traditional liquid–liquid extraction, the new extraction processes have advantages of the extraction efficiency high and phase separation rapid. The extraction efficiency was more than 98.5% by one-stage extraction. The chemical titer of erythromycin was over 930 μg/mg. The yield of erythromycin was over 70%.

High yield antibiotic producing mutants of Streptomyces erythreus induced by low energy ion implantation

Conidia of Streptomyces erythreus, an industrial microbe, were implanted by nitrogen ions with energy of 40–60 keV and fluence from 1×1011 to 5×1014 ions/cm2. The logarithm value of survival fraction had good linear relationship with the logarithm value of fluence. Some mutants with a high yield of erythromycin were induced by ion implantation. The yield increment was correlated with the implantation fluence. Compared with the mutation results induced by ultraviolet rays, mutation effects of ion implantation were obvious having higher increasing erythromycin potency and wider mutation spectrum. The spores of Bacillus subtilis were implanted by arsenic ions with energy of 100 keV. The distribution of implanted ions was measured by Rutherford Backscattering Spectrometry (RBS) and calculated in theory. The mechanism of mutation induced by ion implantation was discussed.