ValC, a New Type of C7-Cyclitol Kinase Involved in the Biosynthesis of the Antifungal Agent Validamycin A

✍ Scribed by Kazuyuki Minagawa; Yirong Zhang; Takuya Ito; Linquan Bai; Zixin Deng; Taifo Mahmud

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 633 KB
• Volume: 8
• Category: Article
• ISSN: 1439-4227
• DOI: 10.1002/cbic.200600528

✦ Synopsis

Abstract

The gene valC, which encodes an enzyme homologous to the 2‐epi‐5‐epi‐valiolone kinase (AcbM) of the acarbose biosynthetic pathway, was identified in the validamycin A biosynthetic gene cluster. Inactivation of valC resulted in mutants that lack the ability to produce validamycin A. Complementation experiments with a replicating plasmid harboring full‐length valC restored the production of validamycin A, thus suggesting a critical function of valC in validamycin biosynthesis. In vitro characterization of ValC revealed a new type of C7‐cyclitol kinase, which phosphorylates valienone and validone—but not 2‐epi‐5‐epi‐valiolone, 5‐epi‐valiolone, or glucose—to afford their 7‐phosphate derivatives. The results provide new insights into the activity of this enzyme and also confirm the existence of two different pathways leading to the same end‐product: the valienamine moiety common to acarbose and validamycin A.