Uncovering the specificity and predictability of tryptophan metabolism in lactic acid bacteria with genomics and metabolomics

Tong Pan; Zhangming Pei; Zhifeng Fang; Hongchao Wang; Jinlin Zhu; Hao Zhang; Jianxin Zhao; Wei Chen; Wenwei Lu

doi:10.3389/fcimb.2023.1154346

Uncovering the specificity and predictability of tryptophan metabolism in lactic acid bacteria with genomics and metabolomics

Front Cell Infect Microbiol. 2023 Mar 13:13:1154346. doi: 10.3389/fcimb.2023.1154346. eCollection 2023.

Authors

Tong Pan^{1

2}, Zhangming Pei^{1

2}, Zhifeng Fang³, Hongchao Wang^{1

2}, Jinlin Zhu^{1

2}, Hao Zhang^{1

2

4

5}, Jianxin Zhao^{1

2

5}, Wei Chen^{1

2

4}, Wenwei Lu^{1

2

4

5

6}

Affiliations

¹ State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China.
² School of Food Science and Technology, Jiangnan University, Wuxi, China.
³ School of Food Science and Technology, Shihezi University, Shihezi, China.
⁴ National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, China.
⁵ (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou, China.
⁶ International Joint Research Laboratory for Pharmabiotics & Antibiotic Resistance, Jiangnan University, Wuxi, China.

Abstract

Tryptophan is metabolized by microorganisms into various indole derivatives that have been proven to alleviate diseases and promote human health. Lactic acid bacteria (LAB) are a broad microbial concept, some of which have been developed as probiotics. However, the capacity of most LAB to metabolize tryptophan is unknown. In this study, the aim is to reveal the rule of tryptophan metabolism in LAB by multi-omics. The findings showed that LAB were rich in genes for tryptophan catabolism and that multiple genes were shared among LAB species. Although the number of their homologous sequences was different, they could still form the same metabolic enzyme system. The metabolomic analysis revealed that LAB were capable of producing a variety of metabolites. Strains belonging to the same species can produce the same metabolites and have similar yields. A few strains showed strain-specificity in the production of indole-3-lactic acid (ILA), indole-3-acetic acid, and 3-indolealdehyde (IAld). In the genotype-phenotype association analysis, the metabolites of LAB were found to be highly consistent with the outcomes of gene prediction, particularly ILA, indole-3-propionic acid, and indole-3-pyruvic acid. The overall prediction accuracy was more than 87% on average, which indicated the predictability of tryptophan metabolites of LAB. Additionally, genes influenced the concentration of metabolites. The levels of ILA and IAld were significantly correlated with the numbers of aromatic amino acid aminotransferase and amidase, respectively. The unique indolelactate dehydrogenase in Ligilactobacillus salivarius was the primary factor contributing to its large production of ILA. In summary, we demonstrated the gene distribution and production level of tryptophan metabolism in LAB and explored the correlation between genes and phenotypes. The predictability and specificity of the tryptophan metabolites in LAB were proven. These results provide a novel genomic method for the discovery of LAB with tryptophan metabolism potential and offer experimental data for probiotics that produce specific tryptophan metabolites.

Keywords: genomics; lactic acid bacteria; metabolism; metabolomics; predictability; specificity; tryptophan.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Genomics
Humans
Indoles / metabolism
Lactobacillales* / genetics
Lactobacillales* / metabolism
Metabolomics / methods
Tryptophan / metabolism

Substances

Tryptophan
Indoles

Grants and funding

This work was supported by the National Natural Science Foundation of China (No. 31820103010, 31972085, 32202059), 111project (BP0719028), and the collaborative innovation center of food safety and quality control in Jiangsu Province.