sanN encoding a dehydrogenase is essential for Nikkomycin biosynthesis in Streptomyces ansochromogenes.
Nikkomycins are a group of peptidyl nucleoside antibiotics with potent fungicidal, insecticidal, and acaricidal activities. sanN was cloned from the partial genomic library of Streptomyces ansochromogenes 7100. Gene disruption and complementation analysis demonstrated that sanN is essential for nikkomycin biosynthesis in S. ansochromogenes. Primer extension assay indicated that sanN is transcribed from two promoters (sanN-P1 and sanN-P2), and sanN-P2 plays a more important role in nikkomycin biosynthesis. Purified recombinant SanN acts as a dehydrogenase to convert benzoate-CoA to benzaldehyde in a random-order mechanism in vitro, with respective Kcat/Km values of 3.8 mM-1s-1 and 12.0 mM-1s-1 toward benzoate-CoA and NADH, suggesting that SanN catalyzes the formation of picolinaldehyde during biosynthesis of nikkomycin X and Z components in the wild-type stain. These data would facilitate us to understand the biosynthetic pathway of nikkomycins and to consider the combinatorial synthesis of novel antibiotic derivatives.
Ling
Hong-Bo
HB
State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Wang
Guo-Jun
GJ
Li
Jin-E
JE
Tan
Hua-Rong
HR
D000617:Aminoglycosides / Q000032:analysis / Q000096:biosynthesis*; D000900:Anti-Bacterial Agents / Q000032:analysis / Q000096:biosynthesis*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D053898:Biosynthetic Pathways; D002681:China; D003001:Cloning, Molecular; D015870:Gene Expression; D005816:Genetic Complementation Test; D007700:Kinetics; D008969:Molecular Sequence Data; D010088:Oxidoreductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D012988:Soil Microbiology; D013302:Streptomyces / Q000201:enzymology* / Q000235:genetics; D024363:Transcription Initiation Site
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C011952:nikkomycin; D010088:Oxidoreductases