Details

Autor(en) / Beteiligte

• ALONSO, M. J.
• BERMEJO, F.
• REGLERO, A.
• FERNÁNDEZ-CANÓN, J. M.
• BUITRAGO, G. GONZÁLEZ DE
• LUENGO, J. M.

Titel

ENZYMATIC SYNTHESIS OF PENICILLINS

Ist Teil von

• The Journal of Antibiotics, 1988/08/25, Vol.41(8), pp.1074-1084

Ort / Verlag

Tokyo: JAPAN ANTIBIOTICS RESEARCH ASSOCIATION

Erscheinungsjahr

1988

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• Different penicillins (phenylacetyl, 2-hydroxyphenylacetyl, 4-hydroxyphenylacetyl, phenoxyacetyl and 2-thiopheneacetylpenicillin) have been synthesized "in vitro" by direct N-acylation of 6-aminopenicillanic acid (6-APA) with the acyl group of several acyl-CoA derivatives. The enzyme that catalyzes these reactions, acyl-CoA: 6-APA acyltransferase of Penicillium chrysogenum, was purified to homogeneity (374-fold) and its amino acid composition is given. This protein accepts as substrates several aliphatic acids and different aromatic acids with the only requirement that an acetyl-CoA moiety must be present in the substrate molecule. Shortening or lengthening of the acyl moiety prevents the 6-APA-Nacylation reaction. The presence of an amino group in the α-position of the acetyl group does not allow this molecule to be used as substrate. However, different substitutions in the phenyl group (hydroxylation of the carbons 2 and 4) or its replacement by another aromatic ring (thiophene) were accepted with varying reactions rates in the acylation reaction when a 176-fold purified acyltransferase was employed. The homogeneity pure enzyme accepts as substrate thiophene acetyl-CoA but it did not 2-hydroxyphenyl and 4-hydroxyphenylacetyl-CoA. The presence of an oxygen atom between the aromatic and the acetyl moieties did not affect the catalysis.