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Review
. 2025 Jun 4:13:1585736.
doi: 10.3389/fbioe.2025.1585736. eCollection 2025.

Enzymatic approaches to nicotinic acid synthesis: recent advances and future prospects

Rahul Vikram Singh  1 , Vipin Chandra Kalia  1 , Krishika Sambyal  1 , Bakul Singh  1 , Anurag Kumar  1 , Jung-Kul Lee  1
Affiliations
Review

Enzymatic approaches to nicotinic acid synthesis: recent advances and future prospects

Rahul Vikram Singh et al. Front Bioeng Biotechnol. .

Abstract

Biocatalyst-mediated reactions have led to revolutionary transformations in the organic synthesis of pharmaceuticals, drugs, and other chemicals. Nicotinic acid (vitamin B3) is an essential precursor for nicotinamide adenine dinucleotide (NAD+) biosynthesis and is vital for numerous metabolic processes. Since the human body cannot synthesize nicotinic acid, it relies on external sources. Therefore, nicotinic acid synthesis has gained huge attraction. In recent years, the industrial production of nicotinic acid has increasingly shifted from traditional chemical methods to more biocatalytic processes, leveraging the power of biocatalysts. This review highlights the biocatalyst-mediated synthesis of nicotinic-acid- and nitrile-metabolizing enzymes through state-of-the-art omics-based techniques to improve enzyme catalytic efficiency and stability via various approaches. Future research prospects and challenges associated with nicotinic acid production are also discussed.

Keywords: biocatalysis; biotransformation; immobilization; nitrilase; omics technology.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

FIGURE 1
FIGURE 1
Schematic representation of NAD+ synthesis pathways, de novo from tryptophan via the kynurenine pathway or from nicotinic acid via the Preiss–Handler pathway and the salvage pathway from nicotinamide (NAM) (Xie et al., 2020). Abbreviations: IDO, indoleamine 2,3-dioxygenase; QA, quinolinic acid; NAMN, nicotinate mononucleotide; QPRT, quinolinate phosphoribosyl-transferase; NAPRT, nicotinic acid phosphoribosyltransferase; NMNATs, nicotinamide mononucleotide adenylyl transferases; NADSYN, NAD synthase; NR, nicotinamide riboside; Trp, tryptophan; NADKs, NAD+ kinases; PARPs, poly (ADP-ribose) polymerases; NNT, nicotinamide nucleotide transhydrogenase; TDO, tryptophan 2,3-dioxygenase; SARM1, sterile alpha and TIR motif-containing 1; NNMT, Nicotinamide N-methyltransferase; NMN, nicotinamide mononucleotide; PUFAs, polyunsaturated fatty acids; NAM, nicotinamide; ACMSD, alpha-amino-beta-carboxy-muconate-semialdehyde decarboxylase).
FIGURE 2
FIGURE 2
Chemical synthesis of nicotinic acid.
FIGURE 3
FIGURE 3
Enzymatic synthesis. Conversion of nitrile substrates (2-cyanopyridine, 3-cyanopyridine, 4-cyanopyridine) to nicotinic acid by nitrilase or conversion of amide substrates (nicotinamide, isonicotinamide) to nicotinic acid by amidase. Nitrilehydratase (Nhase) converts nitriles to nicotinamide.
FIGURE 4
FIGURE 4
Schematic illustration of the conventional and proposed omics-based approaches for the discovery of enzymes utilized in the synthesis of nicotinic acid (adopted and modified from Barglow et al., 2008; Zhu et al., 2022).
FIGURE 5
FIGURE 5
Representation of enzyme immobilization and a packed reactor.
See this image and copyright information in PMC

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