Lawrence Berkeley National Laboratory
Production of clovamide and its analogs in Saccharomyces cerevisiae and Lactococcus lactis.
- Author(s): Bouchez, Pablo
- Teixeira Benites, Veronica
- Baidoo, Edward EK
- Mortimer, Jenny C
- Sullivan, Michael L
- Scheller, Henrik V
- Eudes, Aymerick
- et al.
Published Web Locationhttps://onlinelibrary.wiley.com/doi/full/10.1111/lam.13190
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 the best of 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. This article is protected by copyright. All rights reserved.