Process development of itaconic acid production by a natural wild type strain of Aspergillus terreus to reach industrially relevant final titers

Abstract

Itaconic acid is a promising organic acid and is commercially produced by submerged fermentation of Aspergillus terreus. The cultivation process of the sensitive filamentous fungus has been studied intensively since 1932, with respect to fermentation media components, oxygen supply, shearing rate, pH value, or culture method. Whereas increased final titers were achieved over the years, the productivity has so far remained quite low. In this study, the impact of the pH on the itaconic acid production was investigated in detail. The pH during the growth and production phase had a significant influence on the final itaconic acid concentration and pellet diameter. The highest itaconic acid concentration of 160 g/L was achieved at a 1.5-L scale within 6.7 days by raising and controlling the pH value to pH 3.4 in the production phase. An ammonia solution and an increased phosphate concentration were used with an itaconic acid yield of 0.46 (w/w) and an overall productivity of 0.99 g/L/h in a fed-batch mode. A cultivation with a lower phosphate concentration resulted in an equal final concentration with an increased yield of 0.58 (w/w) after 11.8 days and an overall productivity of 0.57 g/L/h. This optimized process was successfully transferred from a 1.5-L scale to a 15-L scale. After 9.7 days, comparable pellet morphology and a final concentration of 150 g/L itaconic acid was reached. This paper provides a process strategy to yield a final titer of itaconic acid from a wild-type strain of A. terreus which is in the same range as the well-known citric acid production.

Optimization and scale up of itaconic acid production from potato starch waste in stirred tank bioreactor

“…This is in agreement with certain past studies, which suggested that IA production by A. terreus occurs under phosphate‐limiting condition. However, few recent studies concluded that IA production is not initiated by phosphate limitation and the triggers for IA production remain unknown. This inconsistency may be due the differences in fermentation conditions and A. terreus strains used by different studies.…”

The interplay between transport and metabolism in fungal itaconic acid production

“…The optimal extracellular pH for itaconate production of A. terreus and U. maydis is very different. With A. terreus, itaconic acid is usually produced at a pH below 3.8, and the optimal pH range is mostly governed by limitations in cell morphology and pathway induction (Karaffa et al, 2015;Krull et al, 2017;Kuenz et al, 2012). In contrast, wildtype U. maydis only produces itaconate at a pH above 5.5 (Geiser et al, 2014).…”

“…Some A. terreus strains have also been reported to produce these products (Guevarra & Tabuchi, 1990a;Jadwiga & Diana, 1974), likely through a similar P450 enzyme encoded by the cypC gene directly adjacent to the itaconate gene cluster (Geiser et al, 2016;Steiger et al, 2013). However, (S)-2-hydroxyparaconate production is not reported for strains such as A. terreus NRRL 1960 or A. terreus DSM 23081 (Krull et al, 2017;Kuenz et al, 2012), possibly because these strains were selected by screening for high itaconate production leading to the selection of a defect in cypC expression. Both U. maydis and A. terreus possess a major facilitator superfamily transporter, encoded by Um_itp1 and At_mfsA, which are assumed to be itaconate exporters (Geiser et al, 2016;Hossain et al, 2016;Li et al, 2011).…”

A Review of the Biotechnological Production of Methacrylic Acid

“…Itaconic acid is also produced from citrate through the intermediate cis-aconitate which is decarboxylated to itaconate as illustrated in Figure 1M. Titers in the range of 120-220 g/L have been reported with itaconate yields ranging from 0.45 to as high as 0.58 g itaconic acid/ g glucose and maximal production rates from 0.45 to 1g/L-h (Hevekerl et al, 2014;Huang et al, 2014;Krull et al, 2017a;Tehrani et al, 2019). In addition, the chemical decarboxylation of itaconic acid to MA has been demonstrated via several different catalytic routes, mostly reliant on metal catalysts.…”