Engineering of a probiotic yeast for the production and secretion of medium-chain fatty acids antagonistic to an opportunistic pathogen Candida albicans
is an opportunistic pathogen, with its infection as one of the causes of morbidity or mortality. Notably, the probiotic yeast var. boulardii has shown the potential to fight against infections. In this study, we aimed to engineer a commercial boulardii strain to produce medium-chain fatty acids (MCF...
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Published in | Frontiers in bioengineering and biotechnology Vol. 11; p. 1090501 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
27.02.2023
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Subjects | |
Online Access | Get full text |
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Summary: | is an opportunistic pathogen, with its infection as one of the causes of morbidity or mortality. Notably, the probiotic yeast
var. boulardii has shown the potential to fight against
infections. In this study, we aimed to engineer a commercial boulardii strain to produce medium-chain fatty acids (MCFAs) with antagonistic effects against
. First, we identified and characterized a boulardii strain and created its auxotrophic strain
. Next, we constructed and expressed a heterologous MCFA biosynthetic pathway under the control of inducible and constitutive promoters. Aside from examining MCFA production and secretion, we confirmed MCFAs' effects on
anti-biofilm and anti-hyphal formations and the immunomodulatory effect of MCFA-containing supernatants on Caco-2 cells. We found that under constitutive promoters, the engineered boulardii strain constitutively produced and secreted a mixture of C6:0, C8:0, and C10:0. The secreted MCFAs then reduced biofilm and hyphal formations in
SC5314. We also confirmed that MCFAs upregulated the expression of virulence-related genes in SC5314. Furthermore, we found that the constitutively produced MCFAs in the supernatant induced the upregulation of immune response genes in Caco-2 cells co-cultured with SC5314, indicating MCFAs' roles in immunomodulation. Overall, the engineered boulardii strain produced and secreted MCFAs, as well as demonstrated antagonistic effects against
SC5314 and immune-modulatory effects in Caco-2. To our knowledge, this represents the first study tackling the metabolic engineering of a commercial probiotic yeast strain to constitutively produce and secrete MCFAs showing anti-
effects. Our study forms the basis of the potential development of a live biotherapeutics probiotic yeast against
infections through metabolic engineering strategies. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Ning Xu, Tianjin Institute of Industrial Biotechnology (CAS), China Qilin Yu, Nankai University, China Tao Yu, Shenzhen Institutes of Advanced Technology (CAS), China Edited by: Aiqun Yu, Tianjin University of Science and Technology, China These authors have contributed equally to this work This article was submitted to Synthetic Biology, a section of the journal Frontiers in Bioengineering and Biotechnology Present Address: Hua Ling, Wilmar Innovation Centre, Wilmar International Limited, Singapore, Singapore |
ISSN: | 2296-4185 2296-4185 |
DOI: | 10.3389/fbioe.2023.1090501 |