Abstract
Bile salt hydrolase (BSH) is a well-known enzyme that has been commonly characterized in probiotic bacteria, as it has cholesterol-lowering effects. However, its molecular investigations are scarce. Here, we build a local database of BSH sequences from Lactobacillaceae (BSH–SDL), and phylogenetic analysis and homology searches were employed to elucidate their comparability and distinctiveness among species. Evolutionary study demonstrates that BSH sequences in BSH–SDL are divided into five groups, named BSH A, B, C, D and E here, which can be the genetic basis for BSH classification and nomenclature. Sequence analysis suggests the differences between BSH-active and BSH-inactive proteins clearly, especially on site 82. In addition, a total of 551 BSHs from 107 species are identified from 451 genomes of 158 Lactobacillaceae species. Interestingly, those bacteria carrying various copies of BSH A or B can be predicted to be potential cholesterol-lowering probiotics, based on the results of phylogenetic analysis and the subtypes that those previously reported BSH-active probiotics possess. In summary, this study elaborates the molecular basis of BSH in Lactobacillaceae systematically, and provides a novel methodology as well as a consistent standard for the identification of the BSH subtype. We believe that high-throughput screening can be efficiently applied to the selection of promising candidate BSH-active probiotics, which will advance the development of healthcare products in cholesterol metabolism.
Highlights
Cardiovascular disease (CVD) is one of the main causes of health problems and mortality worldwide [1]
A total of 60 bile salt hydrolase protein sequences in 34 Lactobacillaceae species were collected from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database to build a bile salt hydrolase seed database (BSH–SDL) (Table S1)
Every Bile salt hydrolase (BSH) protein sequence was selected from the representative strain in each species, except that two strains were selected from Lactobacillus johnsonii
Summary
Cardiovascular disease (CVD) is one of the main causes of health problems and mortality worldwide [1]. Multiple risk factors could give rise to CVD, elevated serum cholesterol is the major cause correlating to the progression of CVD in humans. Cholesterol in the human body is absorbed from food in the small intestine or de-novo synthesized in the liver. The two groups within each macromolecular compound are conjugated. These four compounds are accumulated in the body and have been reported to cause adverse effects, including cytotoxicity [5], severe cancer-promoting consequences [6], colonic and oesophageal carcinogenesis in the context of obesity [7,8], and even liver tumour development [9]
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