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Updated: Jan 5, 2026

Enzymatic Cascade Reactions for the Synthesis of Chiral Amino Alcohols from L-lysine
Published on: February 16, 2018
The l-Alanosine Gene Cluster Encodes a Pathway for Diazeniumdiolate Biosynthesis
Tai L Ng1, Monica E McCallum1, Christine R Zheng1
1Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA, 02138, USA.
Abstract:
N-Nitroso-containing natural products are bioactive metabolites with antibacterial and anticancer properties. In particular, compounds containing the diazeniumdiolate (N-nitrosohydroxylamine) group display a wide range of bioactivities ranging from cytotoxicity to metal chelation. Despite the importance of this structural motif, knowledge of its biosynthesis is limited. Herein we describe the discovery of a biosynthetic gene cluster in Streptomyces alanosinicus ATCC 15710 responsible for producing the diazeniumdiolate natural product l-alanosine. Gene disruption and stable isotope feeding experiments identified essential biosynthetic genes and revealed the source of the N-nitroso group. Additional biochemical characterization of the biosynthetic enzymes revealed that the non-proteinogenic amino acid l-2,3-diaminopropionic acid (l-Dap) is synthesized and loaded onto a free-standing peptidyl carrier protein (PCP) domain in l-alanosine biosynthesis, which we propose may be a mechanism of handling unstable intermediates generated en route to the diazeniumdiolate. These discoveries will facilitate efforts to determine the biochemistry of diazeniumdiolate formation.
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