Biosynthesis of the unique amino acid side chain of butirosin: Possible protective-group chemistry in an acyl carrier protein-mediated pathway

被引：53

作者：

Li, YY ^{[1
]}

Llewellyn, NM ^{[1
]}

Giri, R ^{[1
]}

Huang, FL ^{[1
]}

Spencer, JB ^{[1
]}

机构：

[1] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England

来源：

CHEMISTRY & BIOLOGY | 2005年 / 12卷 / 06期

基金：

英国生物技术与生命科学研究理事会;

关键词：

D O I：

10.1016/j.chembiol.2005.04.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Butirosins A and B are naturally occurring aminoglycoside antibiotics that have a (2S)-4-amino-2-hydroxybutyrate(AHBA) side chain. Semisynthetic addition of AHBA to clinically valuable aminoglycoside antibiotics has been shown both to improve their pharmacological properties and to prevent their deactivation by a number of aminoglycoside-modifying enzymes involved in bacterial resistance. We report here that the biosynthesis of AHBA from L-glutamate, encoded within a previously identified butirosin biosynthetic gene cluster, proceeds via intermediates tethered to a specific acyl carrier protein (ACID). Five components of the pathway have been purified and characterized, including the ACP (Btrl), an ATP-dependent ligase (Btrl), a pyridoxal phosphate-dependent decarboxylase (BtrK), and a two-component flavin-dependent monooxygenase system (BtrO and the previously unreported BtrV). The proposed biosynthetic pathway includes a gamma-glutamylation of an ACP-derived gamma-aminobutyrate intermediate, possibly a rare example of protective group chemistry in biosynthesis.

引用

页码：665 / 675

页数：11

共 48 条

[1] A 4-AMINO-2-HYDROXYBUTYRATE ACTIVATING ENZYME FROM BUTIROSIN-PRODUCING BACILLUS-CIRCULANS [J].