Synthesis of Alanosine

Isowa, Yoshikazu; Kurita, Hideaki; Ohmori, Muneki; Sato, Masanari; Mori, Katsuharu

doi:10.1246/bcsj.46.1847

“…However, prior work shows that l-alanosine can be synthesized with a higher yield by using butyl nitrite as an organic nitrosylating reagent instead of NaNO 2 in acidic conditions. [34,35] However, we then tested the reaction of NOdonor diethylamine NONOate with l-N 3 -OH-Dap, and we Angewandte Chemie Communications observed significantly higher production of l-alanosine. With this reagent, the optimum pH is at around 6, with production even at pH 9 (Figure S7).…”

mentioning

confidence: 99%

Biosynthesis of the N–N‐Bond‐Containing Compound l‐Alanosine

Wang

¹

,

Niikura

²

,

He

³

et al. 2020

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The formation of a N−N bond is a unique biochemical transformation, and nature employs diverse biosynthetic strategies to activate nitrogen for bond formation. Among molecules that contain a N−N bond, biosynthetic routes to diazeniumdiolates remain enigmatic. We here report the biosynthetic pathway for the diazeniumdiolate‐containing amino acid l‐alanosine. Our work reveals that the two nitrogen atoms in the diazeniumdiolate of l‐alanosine arise from glutamic acid and aspartic acid, and we clarify the early steps of the biosynthetic pathway by using both in vitro and in vivo approaches. Our work demonstrates a peptidyl‐carrier‐protein‐based mechanism for activation of the precursor l‐diaminopropionate, and we also show that nitric oxide can participate in non‐enzymatic diazeniumdiolate formation. Furthermore, we demonstrate that the gene alnA, which encodes a fusion protein with an N‐terminal cupin domain and a C‐terminal AraC‐like DNA‐binding domain, is required for alanosine biosynthesis.

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“…This reaction is likely to proceed via the nitrosonium ion, the production of which is thought to require acidic conditions. However, prior work shows that l ‐alanosine can be synthesized with a higher yield by using butyl nitrite as an organic nitrosylating reagent instead of NaNO 2 in acidic conditions . However, we then tested the reaction of NO‐donor diethylamine NONOate with l ‐ N 3 ‐OH‐Dap, and we observed significantly higher production of l ‐alanosine.…”

Section: Figurementioning

confidence: 87%

Biosynthesis of the N–N‐Bond‐Containing Compound l‐Alanosine

Wang

¹

,

Niikura

²

,

He

³

et al. 2020

View full text Add to dashboard Cite

The formation of a N−N bond is a unique biochemical transformation, and nature employs diverse biosynthetic strategies to activate nitrogen for bond formation. Among molecules that contain a N−N bond, biosynthetic routes to diazeniumdiolates remain enigmatic. We here report the biosynthetic pathway for the diazeniumdiolate‐containing amino acid l‐alanosine. Our work reveals that the two nitrogen atoms in the diazeniumdiolate of l‐alanosine arise from glutamic acid and aspartic acid, and we clarify the early steps of the biosynthetic pathway by using both in vitro and in vivo approaches. Our work demonstrates a peptidyl‐carrier‐protein‐based mechanism for activation of the precursor l‐diaminopropionate, and we also show that nitric oxide can participate in non‐enzymatic diazeniumdiolate formation. Furthermore, we demonstrate that the gene alnA, which encodes a fusion protein with an N‐terminal cupin domain and a C‐terminal AraC‐like DNA‐binding domain, is required for alanosine biosynthesis.

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“…In fact, besides the expected deprotected hydroxyamino derivative 5 (65%), obtained as the corresponding dihydrochloride and identified on the basis of its NMR properties (vide infra), the over‐reduction product ( S )‐2,3‐diaminopropanoic acid ( 10 , 35%) was also present, also in its dihydrochloride form, which was identified by comparison with a commercial authentic sample. ( S )‐2‐Amino‐3‐(hydroxyamino)propanoic Acid (5) Dihydrochloride: 13c,15 1 H NMR (D 2 O, spectral reference = 2853.00 Hz): δ = 4.42 (dd, J AX = 6.4, J BX = 5.3 Hz, 1 H, CH 2 −C H ), 3.38 (dd, J AB = 14.6, J BX = 5.3 Hz, 1 H, CH−C H 2 ), 3.73 (dd, J AB = 14.6, J AX = 6.4 Hz, 1 H, CH−C H 2 ) ppm. 13 C NMR (D 2 O, spectral reference = 3313.00 Hz): δ = 171.7 (C=O), 51.8 (CH 2 ), 51.5 (CH) ppm.…”

Section: Methodsmentioning

confidence: 99%