Nitrile biosynthesis in nature: how and why?

Covering: up to the end of 2023Natural nitriles comprise a small set of secondary metabolites which however show intriguing chemical and functional diversity. Various patterns of nitrile biosynthesis can be seen in animals, plants, and microorganisms with the characteristics of both evolutionary divergence and convergence. These specialized compounds play important roles in nitrogen metabolism, chemical defense against herbivores, predators and pathogens, and inter- and/or intraspecies communications. Here we review the naturally occurring nitrile-forming pathways from a biochemical perspective and discuss the biological and ecological functions conferred by diversified nitrile biosyntheses in different organisms. Elucidation of the mechanisms and evolutionary trajectories of nitrile biosynthesis underpins better understandings of nitrile-related biology, chemistry, and ecology and will ultimately benefit the development of desirable nitrile-forming biocatalysts for practical applications.

• Publication year

  2024

• Venue

  Natural product reports (Print)

• Publication date

  2024-01-09

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.1039/d3np00028aPMID 38193577
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Engineered aldoxime dehydratase to enable the chemoenzymatic conversion of benzyl amines to aromatic nitriles.

  2023cited by this paper
• Nitriles: an attractive approach to the development of covalent inhibitors.

  2023cited by this paper
• A chemical defense deters cannibalism in migratory locusts

  2023cited by this paper
• Database-driven In Silico-Identification and Characterization of Novel Aldoxime Dehydratases.

  2023cited by this paper
• Novel approach toward industrial aromatic nitriles via biocatalysis: From rational enzyme design to sustainable, energy-saving technology platform

  2023cited by this paper
• Identification and characterization of cytochrome P450 CYP77A59 of loquat (Rhaphiolepis bibas) responsible for biosynthesis of phenylacetonitrile, a floral nitrile compound

  2023cited by this paper
• From Tryptophan to Toxin: Nature's Convergent Biosynthetic Strategy to Aetokthonotoxin.

  2022cited by this paper
• Functional expression and regulation of eukaryotic cytochrome P450 enzymes in surrogate microbial cell factories

  2022cited by this paper
• Nickel-catalyzed hydrogenative coupling of nitriles and amines for general amine synthesis

  2022cited by this paper
• The substrate scope of dehydratases in antibiotic biosynthesis and their application in kinetic resolutions.

  2022cited by this paper
• Structural characterization of Linum usitatissimum hydroxynitrile lyase: A new cyanohydrin decomposition mechanism involving a cyano-zinc complex

  2022cited by this paper
• Crystal structural analysis of aldoxime dehydratase from Bacillus sp. OxB-1: Importance of surface residues in optimization for crystallization.

  2022cited by this paper
• Structural and Mechanistic Investigation of the Unusual Metabolism of Nifurtimox

  2022cited by this paper
• Biosynthesis of Isonitrile- and Alkyne-Containing Natural Products.

  2022cited by this paper
• Scanning aldoxime dehydratase sequence space and characterization of a new aldoxime dehydratase from Fusarium vanettenii.

  2022cited by this paper
• Chemical Diversity of Plant Cyanogenic Glycosides: An Overview of Reported Natural Products

  2021cited by this paper
• Variation in production of cyanogenic glucosides during early plant development: A comparison of wild and domesticated sorghum.

  2021cited by this paper
• Cyanide-free synthesis of aromatic nitriles from aldoximes: Discovery and application of a novel heme-containing aldoxime dehydratase.

  2021cited by this paper
• Recent progress on discovery and research of aldoxime dehydratases

  2021cited by this paper
• Rationalizing the Unprecedented Stereochemistry of an Enzymatic Nitrile Synthesis through a Combined Computational and Experimental Approach

  2021cited by this paper
• Chemoenzymatic one-pot reaction from carboxylic acid to nitrile via oxime

  2021cited by this paper
• The Metabolism of Glucosinolates by Gut Microbiota

  2021cited by this paper
• Cyanide as a primordial reductant enables a protometabolic reductive glyoxylate pathway

  2021cited by this paper
• Nitrile Synthesis with Aldoxime Dehydratases: A Biocatalytic Platform with Applications in Asymmetric Synthesis, Bulk Chemicals, and Biorefineries

  2021cited by this paper
• Protein engineering of the aldoxime dehydratase from Bacillus sp. OxB-1 based on a rational sequence alignment approach

  2021cited by this paper
• Nitrile-containing pharmaceuticals: target, mechanism of action, and their SAR studies.

  2021cited by this paper
• Cyanide-Free Enantioselective Catalytic Strategies for the Synthesis of Chiral Nitriles.

  2020cited by this paper
• Discovery and Structural Analysis to Improve the Enantioselectivity of Hydroxynitrile Lyase from Parafontaria laminata Millipedes for (R)-2-Chloromandelonitrile Synthesis

  2020cited by this paper
• R‐hydroxynitrile lyase from the cyanogenic millipede, Chamberlinius hualienensis—A new entry to the carrier protein family Lipocalines

  2020cited by this paper
• Current Understanding toward Isonitrile Group Biosynthesis and Mechanism.

  2020cited by this paper
• Biochemical pathway of benzyl nitrile derived from L-phenylalanine in tea (Camellia sinensis) and its formation in response to postharvest stresses.

  2020cited by this paper
• Aldoxime Dehydratase Mutants as Improved Biocatalysts for a Sustainable Synthesis of Biorenewables-Based 2-Furonitrile

  2020cited by this paper
• Chemoenzymatic Cascades toward Aliphatic Nitriles Starting from Biorenewable Feedstocks

  2020cited by this paper
• Effect of Particle Wettability and Particle Concentration on the Enzymatic Dehydration of n‐Octanaloxime in Pickering Emulsions

  2020cited by this paper
• Glucosinolate Biosynthesis and the Glucosinolate–Myrosinase System in Plant Defense

  2020cited by this paper
• The Role of a Glucosinolate-Derived Nitrile in Plant Immune Responses

  2020cited by this paper
• Heterogeneous Catalysts “on the Move”: Flow Chemistry with Fluid Immobilised (Bio)Catalysts

  2020cited by this paper
• Front Cover: Recent Progress in CO Hydrogenation over Bimetallic Catalysts for Higher Alcohol Synthesis (ChemCatChem 1/2021)

  2020cited by this paper
• Biotransformations in Pure Organic Medium: Organic Solvent‐Labile Enzymes in the Batch and Flow Synthesis of Nitriles

  2019cited by this paper
• The role of CYP71A12 monooxygenase in pathogen-triggered tryptophan metabolism and Arabidopsis immunity.

  2019cited by this paper
• Chemical convergence between plants and insects: biosynthetic origins and functions of common secondary metabolites.

  2019cited by this paper
• Enzymatic Synthesis of Aliphatic Nitriles at a Substrate Loading of up to 1.4 kg/L: A Biocatalytic Record Achieved with a Heme Protein.

  2019cited by this paper
• Albanitriles A-G: Antiprotozoal Polyacetylene Nitriles from a Mycale Marine Sponge.

  2019cited by this paper
• Sequestration and biosynthesis of cyanogenic glucosides in passion vine butterflies and consequences for the diversification of their host plants

  2019cited by this paper
• Structural diversification during glucosinolate breakdown: mechanisms of thiocyanate, epithionitrile and simple nitrile formation

  2019cited by this paper
• Phenylacetonitrile in locusts facilitates an antipredator defense by acting as an olfactory aposematic signal and cyanide precursor

  2019cited by this paper
• 7-Deazaguanine modifications protect phage DNA from host restriction systems

  2019cited by this paper
• Cyanide-free synthesis of an aromatic nitrile from a biorenewable-based aldoxime: Development and application of a recombinant aldoxime dehydratase as a biocatalyst

  2019cited by this paper
• Reconfigured Cyanogenic Glucoside Biosynthesis in Eucalyptus cladocalyx Involves a Cytochrome P450 CYP706C551[OPEN]

  2018cited by this paper
• Overproduction and characterization of the first enzyme of a new aldoxime dehydratase family in Bradyrhizobium sp.

  2018cited by this paper
• Auranthine, a Benzodiazepinone from Penicillium aurantiogriseum: Refined Structure, Absolute Configuration, and Cytotoxicity.

  2018cited by this paper
• Characterization of a novel hydroxynitrile lyase from Nandina domestica Thunb

  2018cited by this paper
• Multiple strategies for pathogen perception by plant immune receptors.

  2018cited by this paper
• Hydroxynitrile lyases from cyanogenic millipedes: molecular cloning, heterologous expression, and whole-cell biocatalysis for the production of (R)-mandelonitrile

  2018cited by this paper
• Nitrile Metabolizing Enzymes in Biocatalysis and Biotransformation

  2018cited by this paper
• Biocatalytic Synthesis of Nitriles through Dehydration of Aldoximes: The Substrate Scope of Aldoxime Dehydratases

  2018cited by this paper
• Oximes: Unrecognized Chameleons in General and Specialized Plant Metabolism.

  2018cited by this paper
• Cyanogenesis in Arthropods: From Chemical Warfare to Nuptial Gifts

  2018cited by this paper
• Engineering yeast for the production of breviscapine by genomic analysis and synthetic biology approaches

  2018cited by this paper
• Kemp Elimination Catalyzed by Naturally Occurring Aldoxime Dehydratases

  2017cited by this paper
• A Nitrile Glucoside and Biflavones from the Leaves of Campylospermum excavatum (Ochnaceae)

  2017cited by this paper
• Enzyme discovery beyond homology: a unique hydroxynitrile lyase in the Bet v1 superfamily

  2017cited by this paper
• A novel cytochrome P450, CYP3201B1, is involved in (R)‐mandelonitrile biosynthesis in a cyanogenic millipede

  2017cited by this paper
• Metabolites profiling reveals for antimicrobial compositional differences and action mechanism in the toothbrushing stick “miswak” Salvadora persica

  2017cited by this paper
• New function of aldoxime dehydratase: Redox catalysis and the formation of an expected product

  2017cited by this paper
• Cyanide-Free and Broadly Applicable Enantioselective Synthetic Platform for Chiral Nitriles through a Biocatalytic Approach.

  2017cited by this paper
• Metabolomics and biochemical approaches link salicylic acid biosynthesis to cyanogenesis in peach plants

  2017cited by this paper
• Long-Chain Alkyl Cyanides: Unprecedented Volatile Compounds Released by Pseudomonas and Micromonospora Bacteria.

  2017cited by this paper
• Arabidopsis NITRILASE 1 Contributes to the Regulation of Root Growth and Development through Modulation of Auxin Biosynthesis in Seedlings

  2017cited by this paper
• Biosynthesis of the leucine derived α-, β- and γ-hydroxynitrile glucosides in barley (Hordeum vulgare L.).

  2016cited by this paper
• A new cyano-substituted anthracycline metabolite from Streptomyces sp. HS-NF-1006

  2016cited by this paper
• Cytochrome P450 CYP71AT96 catalyses the final step of herbivore-induced phenylacetonitrile biosynthesis in the giant knotweed, Fallopia sachalinensis

  2016cited by this paper
• Noncyanogenic Cyanoglucoside Cyclooxygenase Inhibitors from Simmondsia chinensis.

  2016cited by this paper
• The bifurcation of the cyanogenic glucoside and glucosinolate biosynthetic pathways.

  2015cited by this paper
• Discovery and molecular and biocatalytic properties of hydroxynitrile lyase from an invasive millipede, Chamberlinius hualienensis

  2015cited by this paper
• Four New Cyclohexylideneacetonitrile Derivatives from the Hypocotyl of Mangrove (Bruguiera gymnorrhiza)

  2015cited by this paper
• Bacterial cyanogenesis: impact on biotic interactions

  2015cited by this paper
• A recycling pathway for cyanogenic glycosides evidenced by the comparative metabolic profiling in three cyanogenic plant species.

  2015cited by this paper
• Studies on phytochemical, antioxidant, anti-inflammatory and analgesic activities of Euphorbia dracunculoides

  2015cited by this paper
• TRANSCRIPTION ACTIVATOR-LIKE EFFECTOR NUCLEASE-Mediated Generation and Metabolic Analysis of Camalexin-Deficient cyp71a12 cyp71a13 Double Knockout Lines1

  2015cited by this paper
• The chemical defenses of millipedes (diplopoda): Biochemistry, physiology and ecology

  2015cited by this paper
• A Single Enzyme Transforms a Carboxylic Acid into a Nitrile through an Amide Intermediate.

  2015cited by this paper
• The Alpha Subunit of Nitrile Hydratase Is Sufficient for Catalytic Activity and Post-Translational Modification

  2014cited by this paper
• Identification and characterization of CYP79D16 and CYP71AN24 catalyzing the first and second steps in l-phenylalanine-derived cyanogenic glycoside biosynthesis in the Japanese apricot, Prunus mume Sieb. et Zucc.

  2014cited by this paper
• Biosynthetic Pathway for the Cyanide-Free Production of Phenylacetonitrile in Escherichia coli by Utilizing Plant Cytochrome P450 79A2 and Bacterial Aldoxime Dehydratase

  2014cited by this paper
• Discovery of a novel (R)-selective bacterial hydroxynitrile lyase from Acidobacterium capsulatum

  2014cited by this paper
• CYP77A19 and CYP77A20 characterized from Solanum tuberosum oxidize fatty acids in vitro and partially restore the wild phenotype in an Arabidopsis thaliana cutin mutant.

  2014cited by this paper
• Valencene oxidase CYP706M1 from Alaska cedar (Callitropsis nootkatensis)

  2014cited by this paper
• Cyanogenic glycosides: synthesis, physiology, and phenotypic plasticity.

  2014cited by this paper
• Herbivore-induced poplar cytochrome P450 enzymes of the CYP71 family convert aldoximes to nitriles which repel a generalist caterpillar.

  2014cited by this paper
• Chemical Defense Balanced by Sequestration and De Novo Biosynthesis in a Lepidopteran Specialist

  2014cited by this paper
• Indole Alkaloids from Fischerella Inhibit Vertebrate Development in the Zebrafish (Danio rerio) Embryo Model

  2014cited by this paper
• Lactic acid bacteria convert glucosinolates to nitriles efficiently yet differently from enterobacteriaceae.

  2013cited by this paper
• Structures and comparative characterization of biosynthetic gene clusters for cyanosporasides, enediyne-derived natural products from marine actinomycetes.

  2013cited by this paper
• Two Herbivore-Induced Cytochrome P450 Enzymes CYP79D6 and CYP79D7 Catalyze the Formation of Volatile Aldoximes Involved in Poplar Defense[C][W]

  2013cited by this paper
• Crystal structure of aldoxime dehydratase and its catalytic mechanism involved in carbon-nitrogen triple-bond synthesis

  2013cited by this paper
• Male-to-female transfer of 5-hydroxytryptophan glucoside during mating in Zygaena filipendulae (Lepidoptera).

  2013cited by this paper
• Cytochrome P450‐encoding genes from the Heliconius genome as candidates for cyanogenesis

  2013cited by this paper
• Evolution of specifier proteins in glucosinolate-containing plants

  2012cited by this paper
• Photochemical oxazole-nitrile conversion downstream of rhizoxin biosynthesis and its impact on antimitotic activity.

  2012cited by this paper

• Unveiling the molecular dynamics of a nitrile-containing 5-lipoxygenase-activating protein antagonist in primary macrophages through Raman spectroscopy

  2026cites this paper
• Steroidal Compounds at the Crossroads of Inflammation and Cancer: Implications for Drug Discovery and Therapy

  2026cites this paper
• Photoredox-catalyzed three-component cyanoalkylation of glycine derivatives: Enabled by dual nitrogen-centered radicals

  2026cites this paper
• Regioselective Hydrocyanation of Internal Alkynes Enabled by a Transition-Metal-Free Dual-Catalytic System.

  2025cites this paper
• Fundamental Chemistry and Functional Mechanisms of Nitrile‐Based Electrolyte in Advanced Battery Systems

  2025cites this paper
• Cyano-containing Daphniphyllum alkaloids with antienteroviral activity from the leaves and stems of Daphniphyllum calycinum Benth.

  2025cites this paper
• tert-BuONO-Promoted Nitrosation of 4-Nitroisoxazole-Based Enamines: Synthesis of 5-Cyanoisoxazoles and Their Application.

  2025cites this paper
• OSMAC-Driven Discovery of Six New Alkaloids from the Cold-Seep-Derived Fungus Talaromyces amestolkiae HDN21-0307

  2025influential citation
• Antibacterial and Cytotoxic Decahydrofluorene-Class Alkaloids from the Marine-Derived Fungus Penicillium sp. SCSIO 41512.

  2025cites this paper
• Solvent-controlled silver catalyzed radical transformation of α-imino-oxy acids with cyclic aldimines.

  2025cites this paper
• Green synthesis of benzimidazoles via the palladium catalyzed one-pot reductive coupling of nitroarylamines with nitriles

  2025cites this paper
• Palladium-Catalyzed Enantioselective Ring-Opening/Cyanation of Cyclobutanones.

  2025cites this paper
• Quinazolinone nitriles and related metabolites from the deep-sea-derived fungus Penicillium viridicatum MCCC 3A00265.

  2024cites this paper
• Nickel-catalyzed Reductive Hydrolysis of Nitriles to Alcohols.

  2024cites this paper
• Aldoxime dehydratases: production, immobilization, and use in multistep processes

  2024cites this paper
• Ceratinadin G, a new psammaplysin derivative possessing a cyano group from a sponge of the genus Pseudoceratina

  2024cites this paper
• Photoredox/copper-catalyzed gem-difluoroalkylation-cyanation of 1,3-enynes.

  2024cites this paper