Monascus ruber as cell factory for lactic acid production at low pH

Ruud A. Weusthuis; Astrid E. Mars; Jan Springer; Emil J.H. Wolbert; Hetty van der Wal; Truus G. de Vrije; Mark Levisson; Audrey Leprince; Bwee Houweling-Tan; Antoine Moers; Sjon N.A. Hendriks; Odette Mendes; Yvonne Griekspoor; Marc W.T. Werten; Peter J. Schaap; John van der Oost; Gerrit Eggink

doi:10.1016/j.ymben.2017.05.005

Monascus ruber as cell factory for lactic acid production at low pH

Ruud A. Weusthuis^*, Astrid E. Mars, Jan Springer, Emil J.H. Wolbert, Hetty van der Wal, Truus G. de Vrije, Mark Levisson, Audrey Leprince, Bwee Houweling-Tan, Antoine Moers, Sjon N.A. Hendriks, Odette Mendes, Yvonne Griekspoor, Marc W.T. Werten, Peter J. Schaap, John van der Oost, Gerrit Eggink

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

6 Citations (Scopus)

Abstract

A Monascus ruber strain was isolated that was able to grow on mineral medium at high sugar concentrations and 175 g/l lactic acid at pH 2.8. Its genome and transcriptomes were sequenced and annotated. Genes encoding lactate dehydrogenase (LDH) were introduced to accomplish lactic acid production and two genes encoding pyruvate decarboxylase (PDC) were knocked out to subdue ethanol formation. The strain preferred lactic acid to glucose as carbon source, which hampered glucose consumption and therefore also lactic acid production. Lactic acid consumption was stopped by knocking out 4 cytochrome-dependent LDH (CLDH) genes, and evolutionary engineering was used to increase the glucose consumption rate. Application of this strain in a fed-batch fermentation resulted in a maximum lactic acid titer of 190 g/l at pH 3.8 and 129 g/l at pH 2.8, respectively 1.7 and 2.2 times higher than reported in literature before. Yield and productivity were on par with the best strains described in literature for lactic acid production at low pH.

Original language	English
Pages (from-to)	66-73
Journal	Metabolic Engineering
Volume	42
DOIs	https://doi.org/10.1016/j.ymben.2017.05.005
Publication status	Published - 2017

Keywords

Evolutionary engineering
Genetic engineering
Lactic acid production at low pH
Monascus ruber
Strain isolation

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Monascus ruber as cell factory for lactic acid production at low pH
Weusthuis, R. (Creator), Mars, A. (Creator), Springer, J. (Creator), Wolbert, E. (Creator), van der Wal, H. (Creator), de Vrije, T. (Creator), Levisson, M. (Creator), Leprince, A. (Creator), Houweling-Tan, G. B. N. (Creator), Moers, A. P. H. A. (Creator), Hendriks, S. (Creator), Mendes, O. (Creator), Griekspoor, Y. (Creator), Werten, M. W. T. (Creator), Schaap, P. (Creator), van der Oost, J. (Creator) & Eggink, G. (Creator), Wageningen University, 29 Jun 2017
https://www.ebi.ac.uk/ena/data/view/PRJEB20852
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Weusthuis, R. A., Mars, A. E., Springer, J., Wolbert, E. J. H., van der Wal, H., de Vrije, T. G., Levisson, M., Leprince, A., Houweling-Tan, B., Moers, A., Hendriks, S. N. A., Mendes, O., Griekspoor, Y., Werten, M. W. T., Schaap, P. J., van der Oost, J., & Eggink, G. (2017). Monascus ruber as cell factory for lactic acid production at low pH. Metabolic Engineering, 42, 66-73. https://doi.org/10.1016/j.ymben.2017.05.005

Weusthuis, Ruud A. ; Mars, Astrid E. ; Springer, Jan ; Wolbert, Emil J.H. ; van der Wal, Hetty ; de Vrije, Truus G. ; Levisson, Mark ; Leprince, Audrey ; Houweling-Tan, Bwee ; Moers, Antoine ; Hendriks, Sjon N.A. ; Mendes, Odette ; Griekspoor, Yvonne ; Werten, Marc W.T. ; Schaap, Peter J. ; van der Oost, John ; Eggink, Gerrit. / Monascus ruber as cell factory for lactic acid production at low pH. In: Metabolic Engineering. 2017 ; Vol. 42. pp. 66-73.

@article{aa17c52224784e809fb826a0f1b06a22,

title = "Monascus ruber as cell factory for lactic acid production at low pH",

abstract = "A Monascus ruber strain was isolated that was able to grow on mineral medium at high sugar concentrations and 175 g/l lactic acid at pH 2.8. Its genome and transcriptomes were sequenced and annotated. Genes encoding lactate dehydrogenase (LDH) were introduced to accomplish lactic acid production and two genes encoding pyruvate decarboxylase (PDC) were knocked out to subdue ethanol formation. The strain preferred lactic acid to glucose as carbon source, which hampered glucose consumption and therefore also lactic acid production. Lactic acid consumption was stopped by knocking out 4 cytochrome-dependent LDH (CLDH) genes, and evolutionary engineering was used to increase the glucose consumption rate. Application of this strain in a fed-batch fermentation resulted in a maximum lactic acid titer of 190 g/l at pH 3.8 and 129 g/l at pH 2.8, respectively 1.7 and 2.2 times higher than reported in literature before. Yield and productivity were on par with the best strains described in literature for lactic acid production at low pH.",

keywords = "Evolutionary engineering, Genetic engineering, Lactic acid production at low pH, Monascus ruber, Strain isolation",

author = "Weusthuis, {Ruud A.} and Mars, {Astrid E.} and Jan Springer and Wolbert, {Emil J.H.} and {van der Wal}, Hetty and {de Vrije}, {Truus G.} and Mark Levisson and Audrey Leprince and Bwee Houweling-Tan and Antoine Moers and Hendriks, {Sjon N.A.} and Odette Mendes and Yvonne Griekspoor and Werten, {Marc W.T.} and Schaap, {Peter J.} and {van der Oost}, John and Gerrit Eggink",

year = "2017",

doi = "10.1016/j.ymben.2017.05.005",

language = "English",

volume = "42",

pages = "66--73",

journal = "Metabolic Engineering",

issn = "1096-7176",

publisher = "Elsevier",

}

Weusthuis, RA , Mars, AE, Springer, J, Wolbert, EJH, van der Wal, H, de Vrije, TG, Levisson, M, Leprince, A, Houweling-Tan, B, Moers, A, Hendriks, SNA , Mendes, O , Griekspoor, Y, Werten, MWT, Schaap, PJ , van der Oost, J & Eggink, G 2017, 'Monascus ruber as cell factory for lactic acid production at low pH', Metabolic Engineering, vol. 42, pp. 66-73. https://doi.org/10.1016/j.ymben.2017.05.005

Monascus ruber as cell factory for lactic acid production at low pH. / Weusthuis, Ruud A.; Mars, Astrid E.; Springer, Jan; Wolbert, Emil J.H.; van der Wal, Hetty; de Vrije, Truus G.; Levisson, Mark; Leprince, Audrey; Houweling-Tan, Bwee; Moers, Antoine; Hendriks, Sjon N.A.; Mendes, Odette ; Griekspoor, Yvonne; Werten, Marc W.T.; Schaap, Peter J.; van der Oost, John; Eggink, Gerrit.

In: Metabolic Engineering, Vol. 42, 2017, p. 66-73.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Monascus ruber as cell factory for lactic acid production at low pH

AU - Weusthuis, Ruud A.

AU - Mars, Astrid E.

AU - Springer, Jan

AU - Wolbert, Emil J.H.

AU - van der Wal, Hetty

AU - de Vrije, Truus G.

AU - Levisson, Mark

AU - Leprince, Audrey

AU - Houweling-Tan, Bwee

AU - Moers, Antoine

AU - Hendriks, Sjon N.A.

AU - Mendes, Odette

AU - Griekspoor, Yvonne

AU - Werten, Marc W.T.

AU - Schaap, Peter J.

AU - van der Oost, John

AU - Eggink, Gerrit

PY - 2017

Y1 - 2017

N2 - A Monascus ruber strain was isolated that was able to grow on mineral medium at high sugar concentrations and 175 g/l lactic acid at pH 2.8. Its genome and transcriptomes were sequenced and annotated. Genes encoding lactate dehydrogenase (LDH) were introduced to accomplish lactic acid production and two genes encoding pyruvate decarboxylase (PDC) were knocked out to subdue ethanol formation. The strain preferred lactic acid to glucose as carbon source, which hampered glucose consumption and therefore also lactic acid production. Lactic acid consumption was stopped by knocking out 4 cytochrome-dependent LDH (CLDH) genes, and evolutionary engineering was used to increase the glucose consumption rate. Application of this strain in a fed-batch fermentation resulted in a maximum lactic acid titer of 190 g/l at pH 3.8 and 129 g/l at pH 2.8, respectively 1.7 and 2.2 times higher than reported in literature before. Yield and productivity were on par with the best strains described in literature for lactic acid production at low pH.

AB - A Monascus ruber strain was isolated that was able to grow on mineral medium at high sugar concentrations and 175 g/l lactic acid at pH 2.8. Its genome and transcriptomes were sequenced and annotated. Genes encoding lactate dehydrogenase (LDH) were introduced to accomplish lactic acid production and two genes encoding pyruvate decarboxylase (PDC) were knocked out to subdue ethanol formation. The strain preferred lactic acid to glucose as carbon source, which hampered glucose consumption and therefore also lactic acid production. Lactic acid consumption was stopped by knocking out 4 cytochrome-dependent LDH (CLDH) genes, and evolutionary engineering was used to increase the glucose consumption rate. Application of this strain in a fed-batch fermentation resulted in a maximum lactic acid titer of 190 g/l at pH 3.8 and 129 g/l at pH 2.8, respectively 1.7 and 2.2 times higher than reported in literature before. Yield and productivity were on par with the best strains described in literature for lactic acid production at low pH.

KW - Evolutionary engineering

KW - Genetic engineering

KW - Lactic acid production at low pH

KW - Monascus ruber

KW - Strain isolation

U2 - 10.1016/j.ymben.2017.05.005

DO - 10.1016/j.ymben.2017.05.005

M3 - Article

AN - SCOPUS:85020252195

VL - 42

SP - 66

EP - 73

JO - Metabolic Engineering

JF - Metabolic Engineering

SN - 1096-7176

ER -