d-Sedoheptulose-7-phosphate is a common precursor for the heptoses of septacidin and hygromycin B
| Autor: | Min Wang, Zhenju Cao, Xuejin Zhao, Chunbo Lou, Yihua Chen, Aihua Zhou, Wenzhao Wang, Zhengyan Guo, Xiangxi Meng, Wei Tang, Pengwei Li, Zhoujie Xie |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Isomerase medicine.disease_cause 01 natural sciences Streptomyces 03 medical and health sciences chemistry.chemical_compound Biosynthesis Gene cluster medicine Escherichia coli Multidisciplinary biology 010405 organic chemistry Chemistry Escherichia coli Proteins Purine Nucleosides Biological Sciences biology.organism_classification Heptoses 0104 chemical sciences Biosynthetic Pathways carbohydrates (lipids) 030104 developmental biology Biochemistry Sedoheptulose 7-phosphate Sugar Phosphates Heterologous expression Hygromycin B |
| Popis: | Seven-carbon-chain–containing sugars exist in several groups of important bacterial natural products. Septacidin represents a group of l-heptopyranoses containing nucleoside antibiotics with antitumor, antifungal, and pain-relief activities. Hygromycin B, an aminoglycoside anthelmintic agent used in swine and poultry farming, represents a group of d-heptopyranoses–containing antibiotics. To date, very little is known about the biosynthesis of these compounds. Here we sequenced the genome of the septacidin producer and identified the septacidin gene cluster by heterologous expression. After determining the boundaries of the septacidin gene cluster, we studied septacidin biosynthesis by in vivo and in vitro experiments and discovered that SepB, SepL, and SepC can convert d-sedoheptulose-7-phosphate (S-7-P) to ADP-l-glycero-β-d-manno-heptose, exemplifying the involvement of ADP-sugar in microbial natural product biosynthesis. Interestingly, septacidin, a secondary metabolite from a gram-positive bacterium, shares the same ADP-heptose biosynthesis pathway with the gram-negative bacterium LPS. In addition, two acyltransferase-encoding genes sepD and sepH, were proposed to be involved in septacidin side-chain formation according to the intermediates accumulated in their mutants. In hygromycin B biosynthesis, an isomerase HygP can recognize S-7-P and convert it to ADP-d-glycero-β-d-altro-heptose together with GmhA and HldE, two enzymes from the Escherichia coli LPS heptose biosynthetic pathway, suggesting that the d-heptopyranose moiety of hygromycin B is also derived from S-7-P. Unlike the other S-7-P isomerases, HygP catalyzes consecutive isomerizations and controls the stereochemistry of both C2 and C3 positions. |
| Databáze: | OpenAIRE |
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