The biosynthetic gene cluster for a monocyclic β-lactam antibiotic, nocardicin A

被引：62

作者：

Gunsior, M ^{[1
]}

Breazeale, SD ^{[1
]}

Lind, AJ ^{[1
]}

Ravel, J ^{[1
]}

Janc, JW ^{[1
]}

Townsend, CA ^{[1
]}

机构：

[1] Johns Hopkins Univ, Dept Chem, Baltimore, MD 21218 USA

来源：

CHEMISTRY & BIOLOGY | 2004年 / 11卷 / 07期

关键词：

D O I：

10.1016/j.chembiol.2004.04.012

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：

The monocyclic beta-lactam antibiotic nocardicin A is related structurally and biologically to the bicyclic beta-lactams comprised of penicillins/cephalosporins, clavams, and carbapenems. Biosynthetic gene clusters are known for each of the latter, but not for monocyclic beta-lactams. A previously cloned gene encoding an enzyme specific to the biosynthetic pathway was used to isolate the nocardicin A cluster from Nocardia uniformis. Sequence analysis revealed the presence of 14 open reading frames involved in antibiotic production, resistance, and export. Among these are a two-protein nonribosomal peptide synthetase system, p-hydroxyphenylglycine biosynthetic genes, an S-adenosylmethionine-dependent 3-amino-3-carboxypropyl transferase (Nat), and a cytochrome P450. Gene disruption mutants of Nat, as well as an activation domain of the NRPS system, led to loss of nocardicin A formation. Several enzymes involved in antibiotic biosynthesis were heterologously overproduced, and biochemical characterization confirmed their proposed activities.

引用

页码：927 / 938

页数：12

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