A logical approach to boost the production
of cytosolic AcCoA via the PDH bypass is the
elimination of ethanol production by deleting
the ADH genes. Li et al. (2014) first demonstrated that the deletion of ADH1 is beneficial
for FA production. Lian et al. (2014) went a step
further and deleted the isoforms ADH1 and
ADH4 with a concomitant deletion of glycerol3-phosphate dehydrogenases GPD1 and GPD2
to prevent accumulation of glycerol, a trait preFig. 14.1 A simplified scheme of precursor supply
pathways for production of acetyl-CoA (AcCoA) derivatives in the cytosol of S. cerevisiae. Only the relevant
pathway intermediates are shown in gray boxes: glucose-6-phosphate (G6P), xylulose 5-phosphate (X5P),
glyceraldehyde-3-phosphate (GAP), pyruvate (PYR),
acetaldehyde (AA), ethanol (EtOH), acetate (AC),
acetyl-phosphate (AcP), citrate (CIT), oxaloacetate
(OAA), and malate (MAL). Solid lines depict singlestep reactions, whereas dashed lines stand for multiple
enzymatic steps. Reversibility of reactions is indicated
by double-headed arrows only if relevant in the context
of AcCoA supply. For reactions that can be catalyzed by
enzymes with different specificities, the generic notation “NAD(P)H” is used; otherwise, the specific cofactor is denoted. For clarity, only the reduced form of the
redox cofactors is shown. The reaction stoichiometries
are not considered, and energy equivalents are shown
only for the AcCoA supply reactions. Enzyme names
are abbreviated as follows: PK phosphoketolase, PTA
phosphotransacetylase, PDC pyruvate decarboxylase,
ALD aldehyde dehydrogenase, mPDH mitochondrial
pyruvate dehydrogenase, cPDH cytosolic pyruvate
dehydrogenase, CS citrate synthase, ACL ATP citrate
lyase, MDH malate dehydrogenase, MAE malic enzyme,
A-ALD acetylating aldehyde dehydrogenase, ACS
acetyl-CoA synthetase; heterologous enzymes are
marked with an asterisk * and endogenous enzymes
that are expressed in a different compartment with an
asterisk in brackets
(
*
)
. Transporters are not shown.
Influx/efflux of (pyro)phosphate, carbon dioxide, and
coenzyme A (CoA) moieties is omitted for clarity
342
L. Baumann et al.
of cytosolic AcCoA via the PDH bypass is the
elimination of ethanol production by deleting
the ADH genes. Li et al. (2014) first demonstrated that the deletion of ADH1 is beneficial
for FA production. Lian et al. (2014) went a step
further and deleted the isoforms ADH1 and
ADH4 with a concomitant deletion of glycerol3-phosphate dehydrogenases GPD1 and GPD2
to prevent accumulation of glycerol, a trait preFig. 14.1 A simplified scheme of precursor supply
pathways for production of acetyl-CoA (AcCoA) derivatives in the cytosol of S. cerevisiae. Only the relevant
pathway intermediates are shown in gray boxes: glucose-6-phosphate (G6P), xylulose 5-phosphate (X5P),
glyceraldehyde-3-phosphate (GAP), pyruvate (PYR),
acetaldehyde (AA), ethanol (EtOH), acetate (AC),
acetyl-phosphate (AcP), citrate (CIT), oxaloacetate
(OAA), and malate (MAL). Solid lines depict singlestep reactions, whereas dashed lines stand for multiple
enzymatic steps. Reversibility of reactions is indicated
by double-headed arrows only if relevant in the context
of AcCoA supply. For reactions that can be catalyzed by
enzymes with different specificities, the generic notation “NAD(P)H” is used; otherwise, the specific cofactor is denoted. For clarity, only the reduced form of the
redox cofactors is shown. The reaction stoichiometries
are not considered, and energy equivalents are shown
only for the AcCoA supply reactions. Enzyme names
are abbreviated as follows: PK phosphoketolase, PTA
phosphotransacetylase, PDC pyruvate decarboxylase,
ALD aldehyde dehydrogenase, mPDH mitochondrial
pyruvate dehydrogenase, cPDH cytosolic pyruvate
dehydrogenase, CS citrate synthase, ACL ATP citrate
lyase, MDH malate dehydrogenase, MAE malic enzyme,
A-ALD acetylating aldehyde dehydrogenase, ACS
acetyl-CoA synthetase; heterologous enzymes are
marked with an asterisk * and endogenous enzymes
that are expressed in a different compartment with an
asterisk in brackets
(
*
)
. Transporters are not shown.
Influx/efflux of (pyro)phosphate, carbon dioxide, and
coenzyme A (CoA) moieties is omitted for clarity
342
L. Baumann et al.