|BOUCHEZ, PABLO - Joint Bioenergy Institute (JBEI)|
|BENITES, VERONICA - Joint Bioenergy Institute (JBEI)|
|BAIDOO, EDWARD - Joint Bioenergy Institute (JBEI)|
|MORTIMER, JENNY - Joint Bioenergy Institute (JBEI)|
|SCHELLER, HENRIK - Joint Bioenergy Institute (JBEI)|
|EUDES, AYMERICK - Joint Bioenergy Institute (JBEI)|
Submitted to: Letters in Applied Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/18/2019
Publication Date: 6/20/2019
Citation: Bouchez, P., Benites, V.T., Baidoo, E.E., Mortimer, J.C., Sullivan, M.L., Scheller, H.V., Eudes, A. 2019. Production of clovamide and its analogs in Saccharomyces cerevisiae and Lactococcus lactis. Letters in Applied Microbiology. https://doi.org/10.1111/lam.13190.
Interpretive Summary: N-hydroxycinnamoyl-L-amino acids such as clovamide are bioactive plant-derived phenolic compounds with health-beneficial effects. Relying on chemical synthesis or direct extraction from plant sources for the supply of these valuable molecules poses challenges to environmental sustainability. As an alternative route, this work demonstrates a potential for the biological synthesis of N-hydroxycinnamoyl-L-amino acids using engineered microbial hosts such as Saccharomyces cerevisiae and Lactococcus lactis. Besides being more eco-friendly, as shown in this work, this approach can also provide more structurally diverse compounds which may offer new methods for their delivery to the human body.
Technical Abstract: Clovamide and its analogs are N-hydroxycinnamoyl-L-amino acids (HHA) that exhibit antioxidant activities. For environmental and economic reasons, biological synthesis of these plant-derived metabolites has garnered interest. In this study, we exploited HDT1, a BAHD acyltransferase recently isolated from red clover, for the production of clovamide and derivatives in S. cerevisiae and L. lactis. HDT1 catalyzes the transfer of hydroxycinnamoyl-coenzyme A (CoA) onto aromatic amino acids. Therefore, by heterologously co-expressing HDT1 with 4-coumarate:CoA ligase (4CL), we succeeded in the biological production of clovamide and more than twenty other HHA, including halogenated ones, upon feeding the engineered microorganisms with various combinations of cinnamates and amino acids. To our knowledge, this is the first report on the biological synthesis of HHA, and more generally, on the synthesis of plant-derived antioxidant phenolic compounds in L. lactis. The production of these health-beneficial metabolites in Generally Recognized As Safe (GRAS) microorganisms such as S. cerevisiae and L. lactis provides new options for their delivery as therapeutics.