NOVEL BIOPROCESSES FOR PREPARING 7-ACA AND 7-ADAC

摘要

Important intermediates for preparingcephalosporin antibiotics, 7-amino-cephalosporanicacid (7-ACA) and 7-aminodeacetylcephalosporanic acid(7-ADAC), are prepared by a novel bioprocess in whicha transformed Penicillium chrysogenum strain iscultured in the presence of an adipate feedstock toproduce adipoyl-6-APA (6-amino penicillanic acid);followed by the in situ expression of the followinggenes with which the P. chrysogenum has beentransformed:1) an expandase gene, e.g., fromCephalosporium acremonium, whose expression productconverts the adipoyl-6-APA by ring expansion toadipoyl-7-ADCA;2) an hydroxylase gene whose expressionproduct converts the 3-methyl side chain ofadipoyl-7-ADCA to 3-hydroxymethyl, to give the firstproduct, 7-aminodeacetylcephalosporanic acid(7-ADAC); and3) an acetyltransferase gene whoseexpression product converts the 3-hydroxymethyl sidechain to the 3-acetyloxymethyl side chain of 7-ACA.The final product, 7-ACA, is then prepared bycleavage of the adipoyl side chain using an adipoylacylase. The entire synthesis, accordingly, iscarried out using bioprocesses, and is efficient andeconomical.