Direct Genetic and Enzymatic Evidence for Oxidative Cyclization in Hygromycin B Biosynthesis

作者：Li, Sicong; Zhang, Jun; Liu, Yuanzhen; Sun, Guo; Deng, Zixin; Sun, Yuhui^*

来源：ACS Chemical Biology, 2018, 13(8): 2203-2210.

DOI：10.1021/acschembio.8b00375

• STREPTOMYCES-VIRIDOCHROMOGENES TU57
• LIPOPOLYSACCHARIDE BIOSYNTHESIS
• AVILAMYCIN BIOSYNTHESIS
• PROTEIN-SYNTHESIS
• COMMON PRECURSOR
• STRUCTURAL BASIS
• ANTIBIOTICS
• IRON
• HYGROSCOPICUS
• INHIBITION

Hygromycin B is an aminoglycoside antibiotic with a structurally distinctive orthoester linkage. Despite its long history of use in industry and in the laboratory, its biosynthesis remains poorly understood. We show here, by in-frame gene deletion in vivo and detailed enzyme characterization in vitro, that formation of the unique orthoester moiety is catalyzed by the alpha-ketoglutarate- and non-heme iron-dependent oxygenase HygX. In addition, we identify HygF as a glycosyltransferase adding UDP-hexose to 2-deoxystreptarnine, HygM as a methyltransferase responsible for N-3 methylation, and HygK as an epimerase. These experimental results and bioinformatic analyses allow a detailed pathway for hygromycin B biosynthesis to be proposed, including the key oxidative cyclization reactions.

• 出版日期2018-8
• 单位武汉大学