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Review
. 2022 Oct 8;38(12):232.
doi: 10.1007/s11274-022-03421-2.

Recent advances in the application of microbial diamine oxidases and other histamine-oxidizing enzymes

Lucas Kettner  1 , Ines Seitl  1 , Lutz Fischer  2
Affiliations
Review

Recent advances in the application of microbial diamine oxidases and other histamine-oxidizing enzymes

Lucas Kettner et al. World J Microbiol Biotechnol. .

Abstract

The consumption of foods fraught with histamine can lead to various allergy-like symptoms if the histamine is not sufficiently degraded in the human body. The degradation occurs primarily in the small intestine, naturally catalyzed by the human diamine oxidase (DAO). An inherent or acquired deficiency in human DAO function causes the accumulation of histamine and subsequent intrusion of histamine into the bloodstream. The histamine exerts its effects acting on different histamine receptors all over the body but also directly in the intestinal lumen. The inability to degrade sufficient amounts of dietary histamine is known as the 'histamine intolerance'. It would be preferable to solve this problem initially by the production of histamine-free or -reduced foods and by the oral supplementation of exogenous DAO supporting the human DAO in the small intestine. For the latter, DAOs from mammalian, herbal and microbial sources may be applicable. Microbial DAOs seem to be the most promising choice due to their possibility of an efficient biotechnological production in suitable microbial hosts. However, their biochemical properties, such as activity and stability under process conditions and substrate selectivity, play important roles for their successful application. This review deals with the advances and challenges of DAOs and other histamine-oxidizing enzymes for their potential application as processing aids for the production of histamine-reduced foods or as orally administered adjuvants to humans who have been eating food fraught with histamine.

Keywords: Biogenic amines; Diamine oxidase; Histamine; Histamine intolerance; Histamine oxidizing enzymes.

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Conflict of interest statement

The authors have no relevant financial or non-financial interests to disclose.

Figures

Fig. 1
Fig. 1
Oxidative deamination of histamine by DAO
Fig. 2
Fig. 2
Partial amino acid alignment of microbial HOX and comparison with the Homo sapiens (human) and Lathyrus sativus (pea) DAO. Blue and red framing indicate active sites (373 (D) = aspartic acid and 461 (Y) = tyrosine) of the human DAO. * = fully conserved residue; : = conservation between groups of strongly similar properties; . = conservation between groups of weakly similar properties. Created with Clustal Omega (Sievers et al. 2011)
Fig. 3
Fig. 3
Substrate selectivity of microbial, vegetal (Lathyrus sativus) and animal (pig) HOX found in literature. ‘Weakly accepted substrate’ (yellow) refers to an enzyme activity of less than 8% compared to the most favored substrate or if the activity/selectivity was described as “weak” in the respective literature. 1(Sekiguchi et al. 2004), 2(Lee and Kim 2013a), 3(Choi et al. 1995),4(Shimizu et al. 1997), 5(Sugawara et al. 2014), 6(Sugawara et al. 2015), 7(Schilling and Lerch 1995), 8(Frébort et al. 1996), 9(Sadeghi et al. 2020), 10(Yamashita et al. 1993), 11(Corpillo et al. 2003),12(Lee et al. 2008), 13(Kettner et al. 2021), 14(Šebela et al. 1998), 15(Schwelberger and Bodner 1997), 16(Hill et al. 1970)
Fig. 4
Fig. 4
Structural formulae of the biogenic amines histamine, tyramine, putrescine, cadaverine and spermidine
Fig. 5
Fig. 5
Microbial, pig and pea HOX, their trivial names as denoted in the respective literature, their optimum pH and the substrate used for the HOX activity determination. 1(Sekiguchi et al. 2004), 2(Lee and Kim 2013a), 3(Shimizu et al. 1997), 4(Sugawara et al. 2014), 5(Sugawara et al. 2015), 6(Frébort et al. 1996), 7(Sadeghi et al. 2020), 8(Yamashita et al. 1993), 9(Corpillo et al. 2003),10(Lee et al. 2008), 11(Kettner et al. 2021), 12(Mondovì et al. 1964), 13(Šebela et al. 1998)
Fig. 6
Fig. 6
Microbial and pig HOX, their trivial names as denoted in the respective literature, their temperature maximum and the substrate used for the HOX activity determination. 1(Lee and Kim 2013a), 2(Sugawara et al. 2014), 3(Sugawara et al. 2015), 4(Sadeghi et al. 2020), 5(Yamashita et al. 1993), 6(Corpillo et al. 2003), 7(Kettner et al. 2021), 8Dapkevicius et al. (2000)
Fig. 7
Fig. 7
Theoretical productivities of microbial, vegetal (pea) and animal (pig) HOX (trivial names as denoted in the respective literature). Productivities are given as theoretical values if histamine was used as the substrate and are calculated from the kinetic data. 1(Kettner et al. 2021), 2(Frébort et al. 1996), 3(Shimizu et al. 1997), 4(Sugawara et al. 2015), 5(Corpillo et al. 2003), 6(Sugawara et al. 2014), 7(Yamashita et al. 1993), 8(Šebela et al. 1998), 9(Kettner et al. 2020)
Fig. 8
Fig. 8
Partial alignment of the amino acid sequences of the HOX from A. globiformis, H. polymorpha, Y. lipolytica and A. niger highlighting conserved cysteine residues that might possibly be involved in the formation of a disulfide bond. * = fully conserved residue; : = conservation between groups of strongly similar properties;. = conservation between groups of weakly similar properties. Created with Clustal Omega (Sievers et al. 2011)
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