The presence of high level of histamine is detrimental to the quality and safety of fish sauce. Therefore, this study aimed to study the ability of extremely halophilic archaea to reduce histamine under high salt condition and to examine the enzyme activity potentially involved. Of 156 extremely halophilic archaea isolated from various salt-fermented fishery products, HDS3-1 from an anchovy fish sauce sample fermented for 3 months, exhibited the highest histamine degradation activity when cultured in halophilic medium containing 5 mM histamine (free-base), followed by HDS1-1, HPC1-2, and HIS40-3, respectively. HDS3-1 was classified as Natrinema gari based on 16S rRNA gene sequence similarities and did not exhibit decarboxylase activity toward all tested amino acids. Based on in vitro cytotoxicity assay, the treatment with whole cell extract of HDS3-1 to all cell lines tested resulted in dose-dependent inhibitions of the cell growth with the IC50 values higher than 250 mu g ml(-1). Histamine-degrading activity of HDS3-1 was located in the intracellular fraction and required 1-methoxy-5-methylphenazinium methylsulfate (PMS) as an electron carrier. The optimal pH, salt concentration, and temperature for histamine degradation were pH 6.5-8, 3.5-5 M NaCl, and 40-55 degrees C, respectively. The activity was fully retained at pH 6.5-9, in the presence of NaCl above 2.5 M, and at temperature lower than 50 degrees C. The results suggested that histamine-degrading activity of HDS3-1 was most likely associated with salt-tolerant and thermo-neutrophilic histamine dehydrogenase. (C) 2009 Elsevier Inc. All rights reserved.