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Review
. 2024 Dec;108(1):105.
doi: 10.1007/s00253-023-12962-x. Epub 2024 Jan 10.

Prospects of formamide as nitrogen source in biotechnological production processes

Lynn S Schwardmann  1   2 , Leonie Benninghaus  1 , Steffen N Lindner  3 , Volker F Wendisch  4
Affiliations
Review

Prospects of formamide as nitrogen source in biotechnological production processes

Lynn S Schwardmann et al. Appl Microbiol Biotechnol. 2024 Dec.

Abstract

This review presents an analysis of formamide, focussing on its occurrence in nature, its functional roles, and its promising applications in the context of the bioeconomy. We discuss the utilization of formamide as an innovative nitrogen source achieved through metabolic engineering. These approaches underscore formamide's potential in supporting growth and production in biotechnological processes. Furthermore, our review illuminates formamide's role as a nitrogen source capable of safeguarding cultivation systems against contamination in non-sterile conditions. This attribute adds an extra layer of practicality to its application, rendering it an attractive candidate for sustainable and resilient industrial practices. Additionally, the article unveils the versatility of formamide as a potential carbon source that could be combined with formate or CO2 assimilation pathways. However, its attributes, i.e., enriched nitrogen content and comparatively limited energy content, led to conclude that formamide is more suitable as a co-substrate and that its use as a sole source of carbon for biomass and bio-production is limited. Through our exploration of formamide's properties and its applications, this review underscores the significance of formamide as valuable resource for a large spectrum of industrial applications. KEY POINTS: • Formidases enable access to formamide as source of nitrogen, carbon, and energy • The formamide/formamidase system supports non-sterile fermentation • The nitrogen source formamide supports production of nitrogenous compounds.

Keywords: C1 carbon source; Formamidase; Formamide; Formate; Nitrogen source; Non-sterile fermentation.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Catabolism of the reduced C1 nitrogen compounds monomethylamine and formamide. Enzymes are boxed in dark grey, liberation of nitrogen as either ammonia or L-glutamate is indicated by boxing in green, linear dissimilation of methanol to carbon dioxide is shaded in light grey, and assimilation of formaldehyde, formate, and carbon dioxide is indicated by blue arrows. Abbreviations: 2 e-, transfer of 2 electrons from various redox cofactors; 2OG, 2-oxoglutarate; AmiF, formamidase (EC 3.5.1.49); FADH, formaldehyde dehydrogenase; FDH, formate dehydrogenase; Glut, L-glutamate; GmaS, γ-glutamylmethylamide synthase (EC 6.3.4.12); MAO, monomethylamine oxidase (EC 1.4.9.1); MDH, methanol dehydrogenase, MGS, N-methylglutamate synthase (operating comparable to either glutamate dehydrogenase (EC 1.4.1.2/3/4) or glutamine oxoglutarate aminotransferase GOGAT (EC 1.4.1.13/14)); MGD, N-methyl-L-glutamate dehydrogenase (EC 1.5.99.5)
Fig. 2
Fig. 2
Phylogenetic tree of formamidase AmiF (H. pylori 26695) homologues depicted with the protein structure of AmiF of H. pylori. The tree includes the 100 most homologous proteins to formamidase AmiF from H. pylori 26695 (HELPY), identified by PSI-BLAST, and 7 further formamidase proteins of biotechnological interest. The identified enzymes are assigned to at least 9 different enzyme classes (outlined) and some lack classification. Labels refer to the host organism, as defined in Tab. S1. The crystal structure 2E2L of AmiF from H. pylori (Hung et al. 2007) is depicted
Fig. 3
Fig. 3
Formamide as a formate source to support growth and production via formate and CO2 assimilation pathway. Schemes illustrate formate (blue) and CO2 (orange) utilization via the reductive Acetyl-CoA pathway, the reductive Glycine pathway, the Serine Cycle, and the Calvin-Benson-Bassham (CBB) cycle (from left to right)
Fig. 4
Fig. 4
Engineering of C. glutamicum for formamide-based production of nitrogenous compounds (A) and for co-cultivation with a formamidase-deficient C. glutamicum strain (B). C. glutamicum was engineered to overexpress formamidase (AmiF) gene from H. pylori 26695 (FORM, blue) to produce L-glutamate, L-lysine, dipicolinic acid, and N-methylphenylalanine in nitrogen-substituted minimal salt medium using glucose and formamide as sole sources of carbon and nitrogen. Ammonium release from formamide hydrolysis by AmiF by a formamidase-positive C. glutamicum strain (FORM) supports growth of a formamidase-deficient C. glutamicum strain (WT) in co-cultivation. For differentiation, strains were overexpressing genes either for the fluorescence protein GfpUV (green) or Crimson (red) (B)
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References

    1. Adande GR, Woolf NJ, Ziurys LM. Observations of interstellar formamide: availability of a prebiotic precursor in the galactic habitable zone. Astrobiology. 2013;13:439–453. doi: 10.1089/ast.2012.0912. - DOI - PMC - PubMed
    1. Alva A, Sabido-Ramos A, Escalante A, Bolívar F. New insights into transport capability of sugars and its impact on growth from novel mutants of Escherichia coli. Appl Microbiol Biotechnol. 2020;104:1463–1479. doi: 10.1007/s00253-019-10335-x. - DOI - PubMed
    1. Ambrosio R, Curatti L. Deferred control of ammonium cross-feeding in a N2-fixing bacterium-microalga artificial consortium. Appl Microbiol Biotechnol. 2021;105:2937–2950. doi: 10.1007/s00253-021-11210-4. - DOI - PubMed
    1. Bamforth CW, O’Connor ML. The isolation of pleiotropic mutants of Pseudomonas aminovorans deficient in the ability to grow on methylamine and an examination of their enzymic constitution. J Gen Microbiol. 1979;110:143–149. doi: 10.1099/00221287-110-1-143. - DOI
    1. Bar-Even A. Formate Assimilation: The metabolic architecture of natural and synthetic pathways. Biochemistry. 2016;55:3851–3863. doi: 10.1021/acs.biochem.6b00495. - DOI - PubMed

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