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Grant support

This research was funded by the Spanish Agencia Estatal de Investigacion (AEI, projects PID2020-119306GB-100 and PID2022-138470NB-I00) and the European Union (the CLASSY project, the Horizon 2020 research and innovation program, Grant Agreement No. 862081; and the CORENET project, supported by the HorizonEurope research and innovation program and the Swiss State Secretariat for Education, Research and Innovation (SERI), Grant Agreement No. 101046294).

Analysis of institutional authors

Nogal, NoemiAuthorLuis-Barrera, JavierAuthorVela-Gallego, SoniaAuthorAguilar-Galindo, FernandoAuthorDe La Escosura, AndresCorresponding Author
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Article

NADH-mediated primordial synthesis of amino acids

Publicated to:Organic Chemistry Frontiers. 11 (7): 1924-1932 - 2024-02-14 11(7), DOI: 10.1039/D4QO00050A

Authors: Nogal, Noemi; Luis-Barrera, Javier; Vela-Gallego, Sonia; Aguilar-Galindo, Fernando; de la Escosura, Andres

Affiliations

Inst Adv Res Chem IAdChem, Madrid 28049, Spain - Author
Univ Autonoma Madrid, Dept Chem, Campus Cantoblanco, Madrid 28049, Spain - Author
Univ Autonoma Madrid, Dept Organ Chem, Campus Cantoblanco, Madrid 28049, Spain - Author

Abstract

The pathways that could explain the abiotic synthesis of amino acids are different from those observed in living organisms, which leaves a gap of knowledge between bottom-up approaches towards the understanding of abiogenesis and studies on the emergence and evolution of metabolism. Finding non-enzymatic versions of current key metabolic reactions represents a powerful strategy to fill such a gap, and the use of natural cofactors can be useful to aid that chemistry in the absence of enzymes. In this direction, herein we describe how NADH mediates the reductive amination of alpha-ketoacids in the presence of ammonia, allowing the production of various amino acids. The reaction occurs at room temperature in ammonium/ammonia solutions at pH > 7, conditions that are compatible with some plausible scenarios on the prebiotic Earth. A combination of NMR and mass spectrometry data with computational calculations supports that the reaction proceeds through a hemiaminal intermediate, which subsequently gets dehydrated into the iminium species. This allows for the overcoming of the low reactivity of NADH as a hydride donor to the carbonyl group of alpha-ketoacids, while the cofactor loses the nicotinamide ring during the process. Overall, these results demonstrate that NADH can assist in the production of amino acids through a route that was postulated as primordial by the chemoautotrophic theory, thus providing a link of continuity with the chemistry of these important building blocks in ancient protometabolism.

Keywords
Alpha-keto acidsNad(+OriginsPrebiotic systems chemistryPrecursorsReductive amination

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Organic Chemistry Frontiers due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2024 there are still no calculated indicators, but in 2023, it was in position 6/58, thus managing to position itself as a Q1 (Primer Cuartil), in the category Chemistry, Organic. Notably, the journal is positioned above the 90th percentile.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2025-05-19:

  • WoS: 4
  • Scopus: 6
  • OpenCitations: 6
Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-05-19:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 18.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 18 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 5.7.
  • The number of mentions on the social network X (formerly Twitter): 8 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (NOGAL RODRIGUEZ, NOEMI) and Last Author (ESCOSURA NAVAZO, ANDRES DE LA).

the author responsible for correspondence tasks has been ESCOSURA NAVAZO, ANDRES DE LA.