Metabolic engineering of Saccharomyces cerevisiae for hydroxytyrosol overproduction directly from glucose

Microbial Biotechnology - Tập 15 Số 5 - Trang 1499-1510 - 2022
Ricardo Bisquert1, Andrés Planells‐Cárcel1, Elena Valera‐García1, José Manuel Guillamón1, Sara Muñiz‐Calvo1
1Departamento de Biotecnología de Alimentos Instituto de Agroquímica y Tecnología de Alimentos IATA‐CSIC Agustín Escardino 7 Paterna Valencia 46980 Spain

Tóm tắt

SummaryHydroxytyrosol (HT) is one of the most powerful dietary antioxidants with numerous applications in different areas, including cosmetics, nutraceuticals and food. In the present work, heterologous hydroxylase complex HpaBC from Escherichia coli was integrated into the Saccharomyces cerevisiae genome in multiple copies. HT productivity was increased by redirecting the metabolic flux towards tyrosol synthesis to avoid exogenous tyrosol or tyrosine supplementation. After evaluating the potential of our selected strain as an HT producer from glucose, we adjusted the medium composition for HT production. The combination of the selected modifications in our engineered strain, combined with culture conditions optimization, resulted in a titre of approximately 375 mg l−1 of HT obtained from shake‐flask fermentation using a minimal synthetic‐defined medium with 160 g l−1 glucose as the sole carbon source. To the best of our knowledge, this is the highest HT concentration produced by an engineered S. cerevisiae strain.

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Tài liệu tham khảo

10.1007/s00253-014-6310-6

10.1007/BF00430446

10.1155/2018/7390751

10.1007/s00253-019-09914-9

10.1093/femsyr/foy017

10.1021/jf0515680

10.1038/s41598-017-02042-2

10.1007/s00253-019-09840-w

10.1128/AEM.02617-16

10.1016/j.ymben.2012.10.003

10.3390/cells9091932

10.18632/oncotarget.13553

10.1002/yea.320090613

10.1002/cber.190704001156

Fantes P.A., 1976, Free tryptophan pool and tryptophan biosynthetic enzymes in Saccharomyces cerevisiae, Arch Biochem Biophys, 214, 207

10.1016/j.foodchem.2011.08.023

10.1007/BF00334771

10.1002/biot.201500143

10.1016/S0076-6879(02)50957-5

10.3389/fbioe.2019.00152

10.1016/j.ymben.2019.09.011

10.1111/1567-1364.12118

10.1073/pnas.240469697

10.1016/0378-1119(90)90351-Q

10.1021/acssynbio.7b00385

10.1016/j.resmic.2009.09.015

10.1111/j.1432-1033.1967.tb00083.x

10.1016/j.ymben.2008.02.002

10.1002/yea.320111109

10.1371/journal.pone.0150394

10.1016/0378-1119(95)00037-7

10.1016/j.foodchem.2019.125646

10.1016/j.copbio.2013.03.023

R Development Core Team, 2019, R: A Language and Environment for Statistical Computing

10.1016/j.ymben.2018.01.001

10.1128/jb.171.3.1245-1253.1989

10.1042/bj0690210

10.1016/j.jbiosc.2015.12.022

10.1186/1471-2164-13-573

10.1002/bit.26037

10.1007/BF00430450

10.1016/j.ymben.2015.06.010

Turck D., 2017, Safety of hydroxytyrosol as a novel food pursuant to Regulation (EC) No 258/97, EFSA J, 15, e04728

10.1021/acs.jafc.9b07610

10.1021/acs.jafc.7b01369

10.1038/s41467-020-14918-5

10.1080/00397911.2010.531369