Biosynthesis of 4-aminoheptose 2-epimers, core structural components of the septacidins and spicamycins

• Published in: Journal of antibiotics Vol. 67; no. 5; pp. 405 - 414
• Main Authors: Price, Neil P J, Furukawa, Takayuki, Cheng, Fang, Qi, Jianzhao, Chen, Wenqing, Crich, David
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2014; Japan Antibiotics Research Assoc; Nature Publishing Group
• Subjects: 631/154/349; 631/326/22/1290; 631/535; 631/92/60; Antibiotics, Antineoplastic - biosynthesis; Bacteriology; Biomedical and Life Sciences; Bioorganic Chemistry; Biosynthesis; Biotechnology & Applied Microbiology; Escherichia coli - metabolism; Gas Chromatography-Mass Spectrometry; Glycine - chemistry; Heptoses - biosynthesis; Heptoses - chemistry; Immunology; Indicators and Reagents; Isotopic enrichment; Life Sciences; Life Sciences & Biomedicine; Magnetic Resonance Spectroscopy; Medicinal Chemistry; Microbiology; Organic Chemistry; original-article; Pharmacology & Pharmacy; Purine Nucleosides - biosynthesis; Science & Technology; Solvents; Spectrometry, Mass, Electrospray Ionization; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Streptomyces - chemistry; synthesis; spicamycin; 4-amino-4-deoxyheptose; septacidin; biosynthetic pathway; ANTITUMOR AGENT SPICAMYCIN; DIFFERENTIATION INDUCERS; ANALOGS; SIALIC-ACID; SULFUR; DECARBOXYLATION; PATHWAY; PROMYELOCYTIC LEUKEMIA-CELLS; HL-60; D-MANNO-HEPTOSE
• ISSN: 0021-8820; 1881-1469
• DOI: 10.1038/ja.2014.15

Septacidins and spicamycins are acylated 4-aminoheptosyl-β- N -glycosides produced by Streptomyces fimbriatus and S. alanosinicus , respectively. Their structures are highly conserved, but differ in the stereochemistry of the 4-aminoheptosyl residues. The origin of this stereochemistry is unknown, but is presumably because of the difference in their biosynthetic pathways. We have synthesized the septacidin 4-aminoheptose to verify the difference between septacidin and spicamycin. Isotopic enrichment studies were undertaken using S. fimbriatus , and show that the septacidin heptose is derived from the pentose phosphate pathway. This indicates conserved pathways leading to the biosynthesis of 4-amino-4-deoxy- L - gluco -heptose or 4-amino-4-deoxy- L - manno -heptose.