期刊
CELL CHEMICAL BIOLOGY
卷 23, 期 8, 页码 935-944出版社
CELL PRESS
DOI: 10.1016/j.chembiol.2016.07.011
关键词
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资金
- 973 program [2012CB721004]
- National Science Foundation of China [31270100]
- Wuhan Youth Chenguang Program of Science and Technology [2015070404010181]
Polyoxin, produced by Streptomcyes cacaoi var. asoensis and Streptomyces aureochromogenes, contains two non-proteinogenic amino acids, carbamoylpolyoxamic acid (CPOAA) and polyoximic acid. Although the CPOAA moiety is highly unusual, its biosynthetic logic has remained enigmatic for decades. Here, we address CPOAA biosynthesis by reconstitution of its pathway. We demonstrated that its biosynthesis is initiated by a versatile N-acetyltransferase, PolN, catalyzing L-glutamate (1) to N-acetyl glutamate (2). Remarkably, we verified that PolM, a previously annotated dehydrogenase, catalyzes an unprecedented tandem reduction of acyl-phosphate to aldehyde, and subsequently to alcohol. We also unveiled a distinctive acetylation cycle catalyzed by PolN to synthesize alpha-amino-delta-hydroxyvaleric acid (6). Finally, we report that PolL is capable of converting a rare sequential hydroxylation of alpha-amino-delta-carbamoylhydroxyvaleric acid (7) to CPOAA. PolL represents an intriguing family of Fe(II)-dependent alpha-ketoglutarate dioxygenase with a cupin fold. These data illustrate several novel enzymatic reactions, and also set a foundation for rational pathway engineering for polyoxin production.
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