E. Succinic Acid
Succinic acid is another very important molecule produced by yeast with a major role as
precursor of many valuable bio-based chemicals. These include biodegradable polyesters,
surfactants, additives in food and agriculture,
pharmaceutical products, dyes, etc. Although
succinic acid is still produced by petrochemical
processes in large part, environmental reasons
and advancements in fermentation and metabolic engineering technologies make bio-based
succinic acid production routes a competitive
and future-oriented alternative (Pinazo et al.
2015). As intermediate in the tricarboxylic
acid (TCA) cycle, succinic acid is synthesized
in almost all microbes, plants, and animals. The
ability of growing at low pH and the availability
of genetic information, metabolic engineering,
and -omics tools make yeast an important production host. By using rational metabolic engineering or systems biology approaches mainly
focused on the TCA cycle and the succinic acid
export, strains and fermentation processes were
generated proving competitiveness with the
current petrochemical production (Ito et al.
2014; Otero et al. 2013; Raab et al. 2010). As
an example for strain engineering, a part of the
metabolic engineering strategy of DSM/
Roquette (former Reverdia) using the succinic
acid-tolerant yeast S. cerevisiae is outlined in
Fig. 13.3.
III. Yeasts for Production of
Secondary Metabolites
Secondary metabolites are usually defined as
organic compounds that are not directly
connected to the growth of the organism. As
such this is a negative definition and so essentially every metabolic product qualifies as secondary metabolite as long as it is not directly
associated to growth. However, usually only
those metabolites are referred to as secondary
metabolites, which are somehow connected to
specific functions like protection, competition,
or interactions with other living organisms.
Often their effect is very specific and their production is restricted to a few species. Unlike
primary metabolites, the absence of secondary
metabolites does not result in the demise of the
organism. The specificity of these molecules in
various contexts makes them interesting for
many applications, in particular for pharmaceuticals or cosmetics but also as food or feed
additives, antibiotics, herbicides or fungicides,
and many more. When microbial cells are the
source of the desired metabolites, they are often
directly useful for mass production of the
desired compounds—for example, fungi for
penicillin production. However, often the metabolites are plant derived, and large-scale production is very expensive or even impossible. In
such cases metabolic engineering of microbial
cells offers a promising alternative. Since the
pathways often involve unusual enzymes and
complicated reactions, yeasts are the preferred
host cells for such metabolic engineering
endeavors.
A. Carotenoids
Carotenoids are among the few secondary
metabolites that are naturally produced by certain yeast species. They are pigments with antioxidant properties and chemically part of the
terpenoid family of compounds, consisting
usually of eight isoprene units (C 40 ). Carotenoids are natural colorants with many pharmaceutical
functions
and
nutraceutical
applications, which make them very valuable.
The most prominent producer of the carotenoid astaxanthin is the heterobasidiomycetous
yeast Xanthophyllomyces dendrorhous (teleomorph of Phaffia rhodozyma). This yeast has
been isolated in the late 1960s from tree exudates in such distant points as Japan and Alaska
(Barredo et al. 2017). Another carotenoid naturally produced by yeast is beta-carotene. The
most prominent genus accumulating betacarotene is Rhodotorula found in a wide variety
of habitats all over the world (Tang et al. 2019).
X. dendrorhous naturally accumulates
astaxanthin in high amounts. With distinct
strains grams per liter of astaxanthin can be
accumulated under appropriate culture conditions. Since this yeast is a natural producer,
324
B. Schmelzer et al.
Succinic acid is another very important molecule produced by yeast with a major role as
precursor of many valuable bio-based chemicals. These include biodegradable polyesters,
surfactants, additives in food and agriculture,
pharmaceutical products, dyes, etc. Although
succinic acid is still produced by petrochemical
processes in large part, environmental reasons
and advancements in fermentation and metabolic engineering technologies make bio-based
succinic acid production routes a competitive
and future-oriented alternative (Pinazo et al.
2015). As intermediate in the tricarboxylic
acid (TCA) cycle, succinic acid is synthesized
in almost all microbes, plants, and animals. The
ability of growing at low pH and the availability
of genetic information, metabolic engineering,
and -omics tools make yeast an important production host. By using rational metabolic engineering or systems biology approaches mainly
focused on the TCA cycle and the succinic acid
export, strains and fermentation processes were
generated proving competitiveness with the
current petrochemical production (Ito et al.
2014; Otero et al. 2013; Raab et al. 2010). As
an example for strain engineering, a part of the
metabolic engineering strategy of DSM/
Roquette (former Reverdia) using the succinic
acid-tolerant yeast S. cerevisiae is outlined in
Fig. 13.3.
III. Yeasts for Production of
Secondary Metabolites
Secondary metabolites are usually defined as
organic compounds that are not directly
connected to the growth of the organism. As
such this is a negative definition and so essentially every metabolic product qualifies as secondary metabolite as long as it is not directly
associated to growth. However, usually only
those metabolites are referred to as secondary
metabolites, which are somehow connected to
specific functions like protection, competition,
or interactions with other living organisms.
Often their effect is very specific and their production is restricted to a few species. Unlike
primary metabolites, the absence of secondary
metabolites does not result in the demise of the
organism. The specificity of these molecules in
various contexts makes them interesting for
many applications, in particular for pharmaceuticals or cosmetics but also as food or feed
additives, antibiotics, herbicides or fungicides,
and many more. When microbial cells are the
source of the desired metabolites, they are often
directly useful for mass production of the
desired compounds—for example, fungi for
penicillin production. However, often the metabolites are plant derived, and large-scale production is very expensive or even impossible. In
such cases metabolic engineering of microbial
cells offers a promising alternative. Since the
pathways often involve unusual enzymes and
complicated reactions, yeasts are the preferred
host cells for such metabolic engineering
endeavors.
A. Carotenoids
Carotenoids are among the few secondary
metabolites that are naturally produced by certain yeast species. They are pigments with antioxidant properties and chemically part of the
terpenoid family of compounds, consisting
usually of eight isoprene units (C 40 ). Carotenoids are natural colorants with many pharmaceutical
functions
and
nutraceutical
applications, which make them very valuable.
The most prominent producer of the carotenoid astaxanthin is the heterobasidiomycetous
yeast Xanthophyllomyces dendrorhous (teleomorph of Phaffia rhodozyma). This yeast has
been isolated in the late 1960s from tree exudates in such distant points as Japan and Alaska
(Barredo et al. 2017). Another carotenoid naturally produced by yeast is beta-carotene. The
most prominent genus accumulating betacarotene is Rhodotorula found in a wide variety
of habitats all over the world (Tang et al. 2019).
X. dendrorhous naturally accumulates
astaxanthin in high amounts. With distinct
strains grams per liter of astaxanthin can be
accumulated under appropriate culture conditions. Since this yeast is a natural producer,
324
B. Schmelzer et al.