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Journal of the American Chemical Society Aug 2023l-Alanosine is a diazeniumdiolate (-nitrosohydroxylamine) antibiotic that inhibits MTAP-deficient tumor cells by blocking adenine biosynthesis. Previous work revealed...
l-Alanosine is a diazeniumdiolate (-nitrosohydroxylamine) antibiotic that inhibits MTAP-deficient tumor cells by blocking adenine biosynthesis. Previous work revealed the early steps in the biosynthesis of l-alanosine. In the present study, we used genome mining to discover two new l-alanosine-producing strains that lack the spartate-itrouccinate pathway genes found in the original l-alanosine producer. Instead, nitrate is reduced with a unique set of nitrate-nitrite reductases. These enzymes are typically used as part of the nitrogen cycle for denitrification or assimilation, and our report here shows how enzymes from the nitrogen cycle can be repurposed for the biosynthesis of specialized metabolites. The widespread distribution of nitric-oxide-producing reductases also indicates a potential for the discovery of new nitric-oxide-derived natural products.
Topics: Nitric Oxide; Nitrates; Oxidoreductases; Nitrite Reductases; Nitrate Reductases
PubMed: 37478476
DOI: 10.1021/jacs.3c04447