Insights into Caerulomycin A Biosynthesis: A Two-Component Monooxygenase CrmH-Catalyzed Oxime Formation
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- 作者：Yiguang Zhu ; Qingbo Zhang ; Sumei Li ; Qinheng Lin ; Peng Fu ; Guangtao Zhang ; Haibo Zhang ; Rong Shi ; Weiming Zhu ; Changsheng Zhang
- 刊名：Journal of the American Chemical Society
- 出版年：2013
- 出版时间：December 18, 2013
- 年：2013
- 卷：135
- 期：50
- 页码：18750-18753
- 全文大小：281K
- 年卷期：v.135,no.50(December 18, 2013)
- ISSN：1520-5126
文摘
The immunosuppressive agent caerulomycin A features a unique 2,2鈥?bipyridine core structure and an unusual oxime functionality. Genetic and biochemical evidence confirms that the oxime formation in caerulomycin A biosynthesis is catalyzed by CrmH, a flavin-dependent two-component monooxygenase that is compatible with multiple flavin reductases, from a primary amine via a N-hydroxylamine intermediate. Structure homologue-guided site-directed mutagenesis studies identify four amino acid residues that are essential for CrmH catalysis. This study provides the first biochemical evidence of a two-component monooxygenase that catalyzes oxime formation.