Submitted Successfully!
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Ver. Summary Created by Modification Content Size Created at Operation
1 + 1317 word(s) 1317 2021-04-15 09:06:11 |
2 format correct Meta information modification 1317 2021-05-27 02:58:42 | |
3 format correct -2 word(s) 1315 2021-05-27 03:13:09 |

Video Upload Options

Do you have a full video?


Are you sure to Delete?
If you have any further questions, please contact Encyclopedia Editorial Office.
Gardini, F. Biogenic Amine Production by LAB. Encyclopedia. Available online: (accessed on 29 November 2023).
Gardini F. Biogenic Amine Production by LAB. Encyclopedia. Available at: Accessed November 29, 2023.
Gardini, Fausto. "Biogenic Amine Production by LAB" Encyclopedia, (accessed November 29, 2023).
Gardini, F.(2021, May 26). Biogenic Amine Production by LAB. In Encyclopedia.
Gardini, Fausto. "Biogenic Amine Production by LAB." Encyclopedia. Web. 26 May, 2021.
Biogenic Amine Production by LAB

Lactic acid bacteria (LAB) are considered important biogenic amine (BA) producers in fermented foods. These compounds derive from amino acid decarboxylation through microbial activities and can cause toxic effects on humans, with symptoms (headache, heart palpitations, vomiting, diarrhea) depending also on individual sensitivity. Many studies have focused on the aminobiogenic potential of LAB associated with fermented foods, taking into consideration the conditions affecting BA accumulation and enzymes/genes involved in the biosynthetic mechanisms.

biogenic amines decarboxylase enzymes lactic acid bacteria

1. Biogenic Amine Toxicity and Physiological Role in Microorganisms

A large number of metabolites, exerting both beneficial and detrimental properties for human health, can be synthetized by microorganisms. Among these, amino acid derivatives produced during bacterial growth and fermentation can interact with human physiology in several ways, showing health-modulating potential [1]. This group includes bioactive compounds such as biogenic amines (BAs), which are responsible for adverse effects and are involved in several pathogenic syndromes [1]. In fact, ingestion of food containing high BA amounts is a risk for consumer health since these compounds can cause headache, heart palpitations, vomiting, diarrhea and hypertensive crises [2][3][4]. However, their toxic effect depends on the type of BA, on individual sensitivity or allergy and on the consumption of monoaminooxidase inhibitory drugs or ethanol, which interact with aminooxidase enzymatic systems responsible for the detoxification process of exogenous BAs [5][6].

According to their chemical structures, BAs can be classified as aromatic (tyramine and 2-phenylethylamine), aliphatic (putrescine, cadaverine, spermine and spermidine) and heterocyclic (histamine and tryptamine) and they are analogous to those naturally found in fresh food products, which exert a physiological role associated with cell growth and proliferation [7][8].

2. Role of LAB in Fermented Food BA Content and Their Decarboxylase Clusters Genetic Organization

BA content in fermented foods is of great interest not only for its potential health concerns but also from an economic point of view. On the other hand, the presence of small concentrations of these compounds in fermented foods is often unavoidable. Moreover, the presence of decarboxylase positive non-starter microorganisms, deriving from raw material and productive environment, often leads to high BA concentrations in fermented foods, especially in those obtained without the use of starter cultures [9][10][11][12]. Although starter cultures are accurately selected for the absence of decarboxylase activity, non-controlled autochthonous LAB involved in ripening process can contribute to BA accumulation. LAB are known to be the most relevant tyramine production. However, the can contribute to the accumulation of histamine and putrescine.

Enterococci are the LAB characterized by the highest tyraminogenic potential. The first tyrosine decarboxylase locus (tdc) described in bacteria was found in Enterococcus faecalis JH2-2 [13]. This cluster has been annotated also in the genome sequence of other LAB [14][15][16][17][18][19]. Marcobal et al. [20] evidenced for all tyramine biosynthetic loci a high similarity in both gene sequence and organization, since this locus usually contains the genes encoding tyrosine decarboxylase (tyrDC), tyrosyl tRNA synthetase (tyrS, located upstream the tyrDC gene), putative tyrosine/tyramine permease (tyrP, located downstream the tyrDC gene) and a Na+/H+ antiporter (nhaC) [9]. The similar organization of different tdc clusters, their distribution, and their high similarity of sequence suggest a horizontal transfer of this cluster from a common source [18]. However, different strains can have different transcriptional organizations of the tdc gene cluster, as demonstrated by reverse transcription polymerase chain reaction (PCR) analyses. In fact, the four complete Open Reading Frame (ORF) can be co-transcribed [21] or tyrS can be transcribed independently and not included in the catabolic operon [22].

The LAB histidine decarboxylases belong to pyruvoil-dependent decarboxylases group and the encoding histidine decarboxylase gene (hdcA) has been identified in several LAB species [23][24][25][26][27][28][29][30][31][32]. The histidine decarboxylase gene clusters (hdc) of Gram positive bacteria usually comprise the decarboxylase gene hdcA and the histidine/histamine antiporter gene hdcP. Frequently, an hdcB gene, involved in the conversion of the histidine decarboxylase proenzyme to the active decarboxylase can be found [33]. Moreover, for lactobacilli, a histidyl-tRNA synthetase (hisS) gene has also been described [25]. The transcriptional studies demonstrated that these genes are located on an operon transcribed as a polycistronic mRNA. However, some authors demonstrated that the antiporter gene is transcribed as a monocistronic RNA and that transcriptional termination structures are present in the intergenic regions of histamine operon in Lactobacillus buchneri [30]. Rossi et al. [26] found that hdcA gene of Streptococcus thermophilus PRI60 was genetically different from the hdcA genes sequenced in other LAB, in agreement with the findings of Calles-Enríquez et al. [25], who reported that hdc cluster of S. thermophilus was more closely related to genera such as Clostridium and Staphylococcus than other LAB. Another interesting feature of hdc gene is its possibility to be located on a plasmid [24]. Lucas et al. [23][34] found that Lentilactobacillus hilgardii 0006, Tetragenococcus muriaticus, and Oenococcus oeni strains showed 99 to 100% identical hdcA- and hdcB-encoded proteins, highlighting the presence of a plasmid-encoded histidine decarboxylase system recently transferred horizontally between bacteria. Furthermore, they found that the hdc gene cluster, responsible for histamine production in Lentilactocacillus hilgardii IOEB 0006, was located on an 80-kb plasmid that proved to be unstable. In fact, the capability to form histamine was lost in relation to the growth conditions.

Depending on the producer bacterium, genes/enzymes involved and the ecological niche from which it originates, two different metabolic routes have been described in LAB for the biosynthesis of putrescine [35][36][37]. The first is a decarboxylation system consisting of an ornithine decarboxylase (ODC) and an ornithine/putrescine exchanger. These enzymes are encoded by a gene cluster containing two adjacent genes: (i) speC encoding a biosynthetic/constitutive form of the ODC enzyme and (ii) potE encoding the transmembrane substrate/product exchanger protein [38][35][39]. Gram positive bacteria, however, have been infrequently reported to possess an ODC enzyme and putrescine-producing LAB strains via the ODC pathway are essentially, although not exclusively, derived from wine environment, belonging to the species Ligilactobacillus saerimneri, Levilactobacillus brevis [38][35], Liquorilactobacillus mali [40], and Oenococcus oeni [41]. In contrast, the agmatine deiminase (AgDI) pathway is relatively frequent in LAB and it is even considered a species trait in some enterococci [42]. This pathway consists of a more complex system, comprising AgDI, a putrescine transcarbamylase, a carbamate kinase, and an agmatine/putrescine exchanger [43][44]. Five genes are grouped in the agmatine deiminase cluster (AgDI): the regulator gene aguR and the metabolic genes aguB, aguD, aguA and aguC (aguBDAC). Linares et al. [45] reported that aguR is constitutively transcribed from its promoter (PaguR) while the catabolic genes are co-transcribed in a single mRNA from the aguB promoter (PaguB) in a divergent orientation. These pathway genes were occasionally detected in a putative acid resistance locus in LAB species [44]. In this locus, the AgDI genes are found adjacent to the genes associated with the tyrosine decarboxylase pathway on the chromosome [21], suggesting the presence of genes for high-alkalinizing routes (such as amino acid decarboxylases) in LAB genome.

3. Main LAB Involved in BA Production in Fermented Foods

All fermented foods are subjected to the risk of BA contamination. Although LAB are considered GRAS (Generally Regarded As Safe) organisms, they can have the capability to produce toxic compounds as BAs. In particular, in fermented foods, NSLAB can accumulate BAs and strains of lactobacilli, enterococci, lactococci, pediococci, streptococci, and leuconostocs have been associated with high levels of these compounds [46]. Genetic studies have revealed that many of these strains harbor genes or operons coding for decarboxylating enzymes or other pathways implicated in BA biosynthesis [20][36]

It is known that this decarboxylase activity provides cell advantages because it allows increasing the environmental pH and leads to the energization of membrane. The genetic clusters responsible for BA production in LAB have been described  can show differences that depend mainly on the species and the strain. Nevertheless, it is interesting to note that the decarboxylation mechanisms constitute an important ecological tool which can favor strain competitiveness in stressful conditions (i.e., acid and nutritional stresses) [35][47][22].

The aminobiogenic ability is strain dependent and the selection of specific LAB starters lacking the pathways for BA accumulation and able to outgrow autochthonous microbiota under production conditions is essential to obtain high quality food with reduced contents of these toxic compounds [48].


  1. Pessione, E.; Cirrincione, S. Bioactive molecules released in food by lactic acid bacteria: Encrypted peptides and biogenic amines. Front. Microbiol. 2016, 7, 876.
  2. Alvarez, M.A.; Moreno-Arribas, M.V. The problem of biogenic amines in fermented foods and the use of potential biogenic amine-degrading microorganisms as a solution. Trends Food Sci. Technol. 2014, 39, 146–155.
  3. Hungerford, J.M. Scombroid poisoning: A review. Toxicon 2010, 56, 231–243.
  4. Shalaby, A.R. Significance of biogenic amines to food safety and human health. Food Res. Int. 1996, 29, 675–690.
  5. Sathyanarayana Rao, T.S.; Yeragani, V.K. Hypertensive crisis and cheese. Indian J. Psychiatry 2009, 51, 65–66.
  6. Silla Santos, M.H. Biogenic amines: Their importance in foods. Int. J. Food Microbiol. 1996, 29, 213–231.
  7. Bover-Cid, S.; Latorre-Moratalla, M.L.; Veciana-Nogués, M.T.; Vidal-Carou, M.C. Biogenic amines. In Encyclopedia of Food Safety; Motarjemi, Y., Moy, G., Todd, E., Eds.; Academic Press: San Diego, CA, USA, 2014; pp. 381–391. ISBN 978-0-12-378613-5.
  8. Halász, A.; Baráth, Á.; Simon-Sarkadi, L.; Holzapfel, W. Biogenic amines and their production by microorganisms in food. Trends Food Sci. Technol. 1994, 5, 42–49.
  9. Linares, D.M.; Martin, M.C.; Ladero, V.; Alvarez, M.A.; Fernández, M. Biogenic amines in dairy products. Crit. Rev. Food Sci. Nutr. 2011, 51, 691–703.
  10. Ruiz-Capillas, C.; Jiménez-Colmenero, F. Biogenic amines in meat and meat products. Crit. Rev. Food Sci. Nutr. 2004, 44, 489–499.
  11. Latorre-Moratalla, M.L.; Bover-Cid, S.; Talon, R.; Garriga, M.; Aymerich, T.; Zanardi, E.; Ianieri, A.; Fraqueza, M.J.; Elias, M.; Drosinos, E.H.; et al. Distribution of aminogenic activity among potential autochthonous starter cultures for dry fermented sausages. J. Food Prot. 2010, 73, 524–525.
  12. Suzzi, G.; Gardini, F. Biogenic amines in dry fermented sausages: A review. Int. J. Food Microbiol. 2003, 88, 41–54.
  13. Connil, N.; Plissoneau, L.; Onno, B.; Pilet, M.F.; Prevost, H.; Dousset, X. Growth of Carnobacterium divergens V41 and production of biogenic amines and divercin V41 in sterile cold-smoked salmon extract at varying temperatures, NaCl levels, and glucose concentrations. J. Food Prot. 2002, 65, 333–338.
  14. Marcobal, A.; de las Rivas, B.; Muñoz, R. First genetic characterization of a bacterial b-phenylethylamine biosynthetic enzyme in Enterococcus faecium RM58. FEMS Microbiol. Lett. 2006, 258, 144–149.
  15. Coton, M.; Coton, E.; Lucas, P.; Lonvaud, A. Identification of the gene encoding a putative tyrosine decarboxylase of Carnobacterium divergens 508. Development of molecular tools for the detection of tyramine-producing bacteria. Food Microbiol. 2004, 21, 125–130.
  16. Ladero, V.; Linares, D.M.; del Rio, B.; Fernández, M.; Martin, M.C.; Alvarez, M.A. Draft genome sequence of the tyramine producer Enterococcus durans strain IPLA 655. Genome Announc. 2013, 1, e00265-13.
  17. Bargossi, E.; Gardini, F.; Gatto, V.; Montanari, C.; Torriani, S.; Tabanelli, G. The capability of tyramine production and correlation between phenotypic and genetic characteristics of Enterococcus faecium and Enterococcus faecalis strains. Front. Microbiol. 2015, 6, 1371.
  18. Fernández, M.; Linares, D.M.; Alvarez, M.A. Sequencing of the tyrosine decarboxylase cluster of Lactococcus lactis IPLA 655 and the development of a PCR method for detecting tyrosine decarboxylating lactic acid bacteria. J. Food Prot. 2004, 67, 2521–2529.
  19. Gatto, V.; Tabanelli, G.; Montanari, C.; Prodomi, V.; Bargossi, E.; Torriani, S.; Gardini, F. Tyrosine decarboxylase activity of Enterococcus mundtii: New insights into phenotypic and genetic aspects. Microb. Biotechnol. 2016, 9, 801–813.
  20. Marcobal, A.; de Las Rivas, B.; Landete, J.M.; Tabera, L.; Muñoz, R. Tyramine and phenylethylamine biosynthesis by food bacteria. Crit. Rev. Food Sci. Nutr. 2012, 52, 448–467.
  21. Lucas, P.; Landete, J.; Coton, M.; Coton, E.; Lonvaud-Funel, A. The tyrosine decarboxylase operon of Lactobacillus brevis IOEB 9809: Characterization and conservation in tyramine-producing bacteria. FEMS Microbiol. Lett. 2003, 229, 65–71.
  22. Perez, M.; Calles-Enríquez, M.; Nes, I.; Martin, M.C.; Fernández, M.; Ladero, V.; Alvarez, M.A. Tyramine biosynthesis is transcriptionally induced at low pH and improves the fitness of Enterococcus faecalis in acidic environments. Appl. Microbiol. Biotechnol. 2015, 99, 3547–3558.
  23. Lucas, P.M.; Wolken, W.A.; Claisse, O.; Lolkema, J.S.; Lonvaud-Funel, A. Histamine-producing pathway encoded on an unstable plasmid in Lactobacillus hilgardii 0006. Appl. Environ. Microbiol. 2005, 7, 1417–1424.
  24. Landete, J.M.; de las Rivas, B.; Marcobal, A.; Muñoz, R. Updated molecular knowledge about histamine biosynthesis by bacteria. Crit. Rev. Food Sci. Nutr. 2008, 48, 697–714.
  25. Calles-Enríquez, M.; Eriksen, B.H.; Andersen, P.S.; Rattray, F.P.; Johansen, A.H.; Fernández, M.; Ladero, V.; Alvarez, M.A. Sequencing and transcriptional analysis of the Streptococcus thermophilus histamine biosynthesis gene cluster: Factors that affect differential hdcA expression. Appl. Environ. Microbiol. 2010, 76, 6231–6238.
  26. Rossi, F.; Gardini, F.; Rizzotti, L.; La Gioia, F.; Tabanelli, G.; Torriani, S. Quantitative analysis of histidine decarboxylase gene (hdcA) transcription and histamine production by Streptococcus thermophilus PRI60 under conditions relevant to cheese making. Appl. Environ. Microbiol. 2011, 77, 2817–2822.
  27. Coton, E.; Rollan, G.C.; Lonvaud-Funel, A. Histidine decarboxylase of Leuconostoc oenos 9204: Purification, kinetic properties, cloning and nucleotide sequence of the hdc gene. J. Appl. Microbiol. 1998, 84, 143–151.
  28. Coton, E.; Coton, M. Multiplex PCR for colony direct detection of Gram-positive histamine- and tyramine-producing bacteria. J. Microbiol. Methods 2005, 63, 296–304.
  29. Konagaya, Y.; Kimura, B.; Ishida, M.; Fujii, T. Purification and properties of a histidine decarboxylase from Tetragenococcus muriaticus, a halophilic lactic acid bacterium. J. Appl. Microbiol. 2002, 92, 1136–1142.
  30. Martin, M.C.; Fernández, M.; Linares, D.M.; Alvarez, M.A. Sequencing, characterization and transcriptional analysis of the histidine decarboxylase operon of Lactobacillus buchneri. Microbiology 2005, 151, 1219–1228.
  31. Satomi, M.; Furushita, M.; Oikawa, H.; Yoshikawa-Takahashi, M.; Yano, Y. Analysis of a 30 kbp plasmid encoding histidine decarboxylase gene in Tetragenococcus halophilus isolated from fish sauce. Int. J. Food Microbiol. 2008, 126, 202–209.
  32. Vanderslice, P.; Copeland, W.C.; Robertus, J.D. Cloning and nucleotide sequence of wild type and a mutant histidine decarboxylase from Lactobacillus 30a. J. Biol. Chem. 1986, 261, 15186–15191.
  33. Trip, H.; Mulder, N.L.; Rattray, F.P.; Lolkema, J.S. HdcB, a novel enzyme catalysing maturation of pyruvoyl-dependent histidine decarboxylase. Mol. Microbiol. 2011, 79, 861–871.
  34. Lucas, P.M.; Claisse, O.; Lonvaud-Funel, A. High frequency of histamine-producing bacteria in the enological environmental and instability of the histidine decarboxylase production phenotype. Appl. Environ. Microbiol. 2008, 74, 811–817.
  35. Romano, A.; Ladero, V.; Alvarez, M.A.; Lucas, P.M. Putrescine production via the ornithine decarboxylation pathway improves the acid stress survival of Lactobacillus brevis and is part of a horizontally transferred acid resistance locus. Int. J. Food Microbiol. 2014, 175, 14–19.
  36. Wunderlichová, L.; Buňková, L.; Koutný, M.; Jančová, P.; Buňka, F. Formation, degradation, and detoxification of putrescine by foodborne bacteria: A review. Compr. Rev. Food Sci. Food Saf. 2014, 13, 1012–1033.
  37. Nannelli, F.; Claisse, O.; Gindreau, E.; de Revel, G.; Lonvaud-Funel, A.; Lucas, P.M. Determination of lactic acid bacteria producing biogenic amines in wine by quantitative PCR methods. Lett. Appl. Microbiol. 2008, 47, 594–599.
  38. Romano, A.; Trip, H.; Lonvaud-Funel, A.; Lolkema, J.S.; Lucas, P.M. Evidence of two functionally distinct ornithine decarboxylation systems in lactic acid bacteria. Appl. Environ. Microbiol. 2012, 78, 1953–1961.
  39. Coton, E.; Mulder, N.; Coton, M.; Pochet, S.; Trip, H.; Lolkema, J.S. Origin of the putrescine-producing ability of the coagulase-negative bacterium Staphylococcus epidermidis 2015B. Appl. Environ. Microbiol. 2010, 76, 5570–5576.
  40. Coton, M.; Romano, A.; Spano, G.; Ziegler, K.; Vetrana, C.; Desmarais, C.; Coton, E. Occurrence of biogenic amine-forming lactic acid bacteria in wine and cider. Food Microbiol. 2010, 27, 1078–1085.
  41. Marcobal, A.; de las Rivas, B.; Moreno-Arribas, M.V.; Munoz, R. Evidence for horizontal gene transfer as origin of putrescine production in Oenococcus oeni RM83. Appl. Environ. Microbiol. 2006, 72, 7954–7958.
  42. Ladero, V.; Fernández, M.; Calles-Enríquez, M.; Sánchez-Llana, E.; Cañedo, E.; Martin, M.C.; Alvarez, M.A. Is the production of the biogenic amines tyramine and putrescine a species-level trait in enterococci? Food Microbiol. 2012, 30, 132–138.
  43. Ladero, V.; Rattray, F.P.; Mayo, B.; Martin, M.C.; Fernández, M.; Alvarez, M.A. Sequencing and transcriptional analysis of the biosynthesis gene cluster of putrescine-producing Lactococcus lactis. Appl. Environ. Microbiol. 2011, 77, 6409–6418.
  44. Lucas, P.M.; Blancato, V.S.; Claisse, O.; Magni, C.; Lolkema, J.S.; Lonvaud-Funel, A. Agmatine deiminase pathway genes in Lactobacillus brevis are linked to the tyrosine decarboxylation operon in a putative acid resistance locus. Microbiology 2007, 153, 2221–2230.
  45. Linares, D.M.; Perez, M.; Ladero, V.; del Rio, B.; Redruello, B.; Martin, M.C.; Fernández, M.; Alvarez, M.A. An agmatine-inducible system for the expression of recombinant proteins in Enterococcus faecalis. Microb. Cell Fact. 2014, 13, 169.
  46. Özogul, F.; Hamed, I. The importance of lactic acid bacteria for the prevention of bacterial growth and their biogenic amines formation: A review. Crit. Rev. Food Sci. Nutr. 2018, 58, 1660–1670.
  47. Pereira, C.I.; Matos, D.; Romão, M.V.S.; Barreto Crespo, M.T. Dual role for the tyrosine decarboxylation pathway in Enterococcus faecium E17: Response to an acid challenge and generation of a proton motive force. Appl. Environ. Microbiol. 2009, 75, 345–352.
  48. Torriani, S.; Felis, G.E.; Fracchetti, F. Selection criteria and tools for malolactic starters development: An update. Ann. Microbiol. 2001, 61, 33–39.
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to :
View Times: 382
Revisions: 3 times (View History)
Update Date: 27 May 2021