Biosynthesis of 3-amino-5-hydroxybenzoic acid, the precursor of mC₇N units in ansamycin antibiotics

verfasst von

Chun Gyu Kim, Andreas Kirschning, Phillipe Bergon, Pei Zhou, Esther Su, Bernd Sauerbrei, Sandra Ning, Yonghyun Ahn, Michael Breuer, Eckhard Leistner, Heinz G. Floss

Abstract

The biosynthetic pathway of 3-amino-5-hydroxybenzoic acid (AHBA) formation was studied with cell-free extracts from the rifamycin B producer, Amycolatopsis mediterranei S699, and the ansatrienin A producer, Streptomyces collinus Tu1892. Phosphoenolpyruvate (PEP) plus erythrose 4-phosphate (E4P) gave AHBA in low but nevertheless significant (6%) yield. 3,4-Dideoxy-4-amino-D-arabino-heptulosonic acid 7-phosphate (aminoDAHP) was converted efficiently into AHBA (45%), as were 5-deoxy-5-amino-3-dehydroquinic acid (aminoDHQ, 41%) and 5-deoxy-5-amino-3-dehydroshikimic acid (aminoDHS, 95%). On the other hand, the normal shikimate pathway intermediate, 3-deoxy-D-arabino-heptulosonic acid 7-phosphate (DAHP) did not give rise to AHBA under these conditions. AminoDAHP (9%) was produced by incubation of [¹⁴C]PEP and E4P, but not of [¹⁴C]DAHP, with the cell-free extracts. The results demonstrate the operation of a new variant of the shikimate pathway in the formation of the mC₇N units of ansamycin, and presumably also mitomycin, antibiotics which leads from PEP, E4P, and a nitrogen source directly to aminoDAHP and then via aminoDHQ and aminoDHS to AHBA.

Externe Organisation(en)

University of Washington
Inje University
Technische Universität Clausthal
Fudan University
Dankook University
Rheinische Friedrich-Wilhelms-Universität Bonn

Typ

Artikel

Journal

Journal of the American Chemical Society

Band

118

Seiten

7486-4791

Anzahl der Seiten

2696

ISSN

0002-7863

Publikationsdatum

14.08.1996

Publikationsstatus

Veröffentlicht

Peer-reviewed

Ja

ASJC Scopus Sachgebiete

Katalyse, Allgemeine Chemie, Biochemie, Kolloid- und Oberflächenchemie

Elektronische Version(en)

https://doi.org/10.1021/ja9601292 (Zugang: Unbekannt)