Butyric Acid

Butyric acid
Butyric acid has industrial applications in the chemicals, plastics, textiles, food,
and pharmaceutical sectors and is now being produced by petroleum sources.
However, the demand for biologically and sustainably produced butyric acid is
growing as consumers want to have organic ingredients in their food,
pharmaceutical, and cosmetic products. Unfortunately, for several biologically-
produced products, including butyric acid, there is a large gap between demand
and supply and this is due to the cost of the process. Butyric acid is biologically
produced by Clostridium species and like other acids (acetic acid, lactic acid,
propionic acid), it is toxic to the bacteria after a certain concentration. Hence, the
product titres are generally low which makes downstream expensive. In order to
reduce these costs, in situ removal of butyric acid can be developed. In situ
removal strategies are not yet industrially applied for butyric acid, but it is a key
area where progress has to be made to make the process economically sustainable.
Butyric acid is produced at the industrial scale via mainly a chemical
synthesis. This involves the oxidation of butyraldehyde, which is obtained from
propylene derived from crude oil by oxosynthesis (Hydroformylation, also known
as oxo synthesis or oxo process, is an industrial process for the production of
aldehydes from alkenes. This chemical reaction entails the net addition of a formyl
group (CHO) and a hydrogen atom to a carbon-carbon double bond). The chemical
synthesis of butyric acid is preferred mainly because of its lower production cost
and the availability of the starting materials. Another method for butyric acid
preparation is its extraction from butter. This is possible since its concentration
in butter ranges from 2% to 4% but the process involved is difficult and expensive
and, thus, cannot compete with the chemical alternative. A third way is through
fermentation. Although this method is currently more expensive compared to
the chemical synthesis, it has garnered more attention due to both a growing
consumer desire for organic and natural products, as opposed to chemically
synthesized ingredients, and a continuous increase in the prices of crude oil, which
is needed for the chemical synthesis as noted earlier.
Strains Available for the Bio-production of Butyric Acid
Under anaerobic conditions, butyric acid is a common metabolite produced by

bacteria strains from various genera. However, for industrial use, Clostridial
strains are preferred owing to their higher productivities and the final
concentrations obtained. The most important Clostridium strains studied for
industrial scale productions of butyric acid are C. butyricum, C. tyrobutyricum,
and C. thermobutyricum. Currently, the most promising microorganism used for
the bioproduction of butyric acid is C. tyrobutyricum. This strain is capable of
producing butyric acid with high selectivity and can tolerate high concentrations
of this compound. However, it can only ferment very few carbohydrates,
including glucose, xylose, fructose, and lactate, while its ability to utilize mannitol
or glycerol is doubtful. On the other hand, C. butyricum can ferment many carbon
sources including hexoses, pentoses, glycerol, lignocellulose, molasses, potato
starch, and cheesewhey permeate. However, compared to C. tyrobutyricum, the
butyrate yields have always been much lower. For C. thermobutyricum, the
range of fermentable sugars is somewhat between these other two strains as it
consumes glucose, fructose, maltose, xylose, ribose, and cellobiose, and some
oligomeric and polymeric sugars but not sucrose or starch.
Butyric Acid Biosynthesis in Clostridium and Factors Affecting Its Production
For the fermentative process to proceed, glucose must first be converted to

pyruvate via the Embden-Meyerhof-Parnas (EMP) pathway, which produces
two moles of ATP and NADH.
Subsequently, pyruvate is fermented to produce several products, depending on the
strain. Lactate dehydrogenase catalyzes the conversion of pyruvate to lactate
while pyruvate-ferredoxin oxidorecuctase catalyzes its conversion to acetyl-

CoA with the release of CO2 and the generation of reduced ferredoxin (fdH2).
For acetate production, phosphotransacetylase (PTA) and acetate kinase (AK) are
the key enzymes while, for butyrate, phosphotransbutyrylase (PTB) and
butyrate kinase (BK) play similar roles.
During acetate production, 4 moles of ATP are formed, while during butyrate
production only 3 moles of ATP are formed, which helps to explain why, at high
growth rates, cells shift more towards acetate rather than butyrate production.
At the end of the exponential growth, the organisms slow down acetate
production and take up excreted acetate, converting it into butyrate. This
recycling may be an attempt of the organism to detoxify the medium by reducing
the total hydrogen ion concentration, that is, acid concentration, as one butyric
acid is produced from two acetic acids. Consequently, the metabolism is shifted
from the more energy conserving acetate formation (1) to a lower acid content with
butyrate formation (2):
Glucose −→ 2 Acetate + 4H2 + 2CO2 + 4ATP (1)
Glucose −→ Butyrate + 2H2 + 2CO2 + 3ATP. (2)
For those strains capable of producing solvents (butanol and acetone), the
fermentation usually passes through two steps—the acidogenesis phase in which
butyric and acetic acids are both produced in the medium and then the
solventogenesis phase in which the organism converts these acids into acetone,
ethanol, and butanol. This second stage is initiated as the medium becomes more
acidic and the cells enter the stationary phase.

Butyric Acid

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Butyric acid

Strains Available for the Bio-production of Butyric Acid

Under anaerobic conditions, butyric acid is a common metabolite produced by

Butyric Acid Biosynthesis in Clostridium and Factors Affecting Its Production

For the fermentative process to proceed, glucose must first be converted to

while pyruvate-ferredoxin oxidorecuctase catalyzes its conversion to acetyl-

Glucose −→ 2 Acetate + 4H2 + 2CO2 + 4ATP (1)

Glucose −→ Butyrate + 2H2 + 2CO2 + 3ATP. (2)

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