title: Highly efficient synthesis of ampicillin in an "aqueous solution-precipitate" system: repetitive addition of substrates in a semicontinuous process.
abstract: The synthesis of ampicillin catalyzed by Escherichia coli penicillin acylase was optimized in an aqueous system with partially dissolved antibiotic nucleus 6-aminopenicillanic acid (6-APA). The yields of both 6-APA and acyl donor could be improved by repetitively adding substrates to the reaction, allowing the concentration of 6-APA to remain saturated throughout. In this reaction concept, with four subsequent additions of substrates, 97% conversion of 6-APA and 72% of D-(-)-phenylglycine methyl ester (D-PGM) to ampicillin was achieved. The synthetic potential of this concept was estimated using a mathematical model which showed that by increasing the amount of added substrates a nearly quantitative conversion of 6-APA and 85% conversion of acyl donor into ampicillin could be achieved.
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119899 Moscow, Russia.
authors.forename: M I
authors.initials: MI
authors.lastname: Youshko
authors.forename: L M
authors.initials: LM
authors.lastname: van Langen
authors.forename: E
authors.initials: E
authors.lastname: de Vroom
authors.forename: F
authors.initials: F
authors.lastname: van Rantwijk
authors.forename: R A
authors.initials: RA
authors.lastname: Sheldon
authors.forename: V K
authors.initials: VK
authors.lastname: Svedas
mesh_terms: D000667:Ampicillin / Q000378:metabolism*; D011232:Chemical Precipitation; D004926:Escherichia coli / Q000201:enzymology; D008962:Models, Theoretical; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D010399:Penicillin Amidase / Q000378:metabolism; D012996:Solutions; D014867:Water
chemical_list: D012996:Solutions; D014867:Water; D000667:Ampicillin; D010397:Penicillanic Acid; D010399:Penicillin Amidase; C004408:aminopenicillanic acid