title: Improved E. coli erythromycin A production through the application of metabolic and bioprocess engineering.
abstract: In this report, small-scale culture and bioreactor experiments were used to compare and improve the heterologous production of the antibiotic erythromycin A across a series of engineered prototype Escherichia coli strains. The original strain, termed BAP1(pBPJW130, pBPJW144, pHZT1, pHZT2, pHZT4, pGro7), was designed to allow full erythromycin A biosynthesis from the exogenous addition of propionate. This strain was then compared against two alternatives hypothesized to increase final product titer. Strain TB3(pBPJW130, pBPJW144, pHZT1, pHZT2, pHZT4, pGro7) is a derivative of BAP1 designed to increase biosynthetic pathway carbon flow as a result of a ygfH deletion; whereas, strain TB3(pBPJW130, pBPJW144, pHZT1, pHZT2, pHZT4-2, pGro7) provided an extra copy of a key deoxysugar glycosyltransferase gene. Production was compared across the three strains with TB3(pBPJW130, pBPJW144, pHZT1, pHZT2, pHZT4, pGro7) showing significant improvement in erythronolide B (EB), 3-mycarosylerythronolide B (MEB), and erythromycin A titers. This strain was further tested in the context of batch bioreactor production experiments with time-course titers leveling at 4 mg/L, representing an approximately sevenfold increase in final erythromycin A titer.
authors: Department of Chemical and Biological Engineering, Tufts University, Medford, MA 02155, USA.
authors: Haoran
authors: H
authors: Zhang
authors: Karin
authors: K
authors: Skalina
authors: Ming
authors: M
authors: Jiang
authors: Blaine A
authors: BA
authors: Pfeifer
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000494:pharmacology; D019149:Bioreactors / Q000382:microbiology; D053898:Biosynthetic Pathways; D003470:Culture Media; D004917:Erythromycin / Q000096:biosynthesis* / Q000494:pharmacology; D004926:Escherichia coli / Q000378:metabolism*; D005285:Fermentation; D010957:Plasmids
chemical_list: D000900:Anti-Bacterial Agents; D003470:Culture Media; D004917:Erythromycin