TY - JOUR

T1 - Squalene production under oxygen limitation by Schizochytrium sp. S31 in different cultivation systems

AU - Schütte, Lina

AU - Hanisch, Patrick G.

AU - Scheler, Nina

AU - Haböck, Katharina C.

AU - Huber, Robert

AU - Ersoy, Franziska

AU - Berger, Ralf G.

N1 - Funding Information: Open Access funding enabled and organized by Projekt DEAL. This research was funded by the German Federal Ministry of Education and Research (SusTerpene, Project 161B0869B). We thank Christoph Schwarz (S2B GmbH & Co. KG, Vechta, Germany) for co-writing the grant proposal and providing the strain Schizochytrium sp. S31.

PY - 2024/2/13

Y1 - 2024/2/13

N2 - Abstract: The triterpene squalene is widely used in the food, cosmetics and pharmaceutical industries due to its antioxidant, antistatic and anti-carcinogenic properties. It is usually obtained from the liver of deep sea sharks, which are facing extinction. Alternative production organisms are marine protists from the family Thraustochytriaceae, which produce and store large quantities of various lipids. Squalene accumulation in thraustochytrids is complex, as it is an intermediate in sterol biosynthesis. Its conversion to squalene 2,3-epoxide is the first step in sterol synthesis and is heavily oxygen dependent. Hence, the oxygen supply during cultivation was investigated in our study. In shake flask cultivations, a reduced oxygen supply led to increased squalene and decreased sterol contents and yields. Oxygen-limited conditions were applied to bioreactor scale, where squalene accumulation and growth of Schizochytrium sp. S31 was determined in batch, fed-batch and continuous cultivation. The highest dry matter (32.03 g/L) was obtained during fed-batch cultivation, whereas batch cultivation yielded the highest biomass productivity (0.2 g/L*h−1). Squalene accumulation benefited from keeping the microorganisms in the growth phase. Therefore, the highest squalene content of 39.67 ± 1.34 mg/g was achieved by continuous cultivation (D = 0.025 h−1) and the highest squalene yield of 1131 mg/L during fed-batch cultivation. Volumetric and specific squalene productivity both reached maxima in the continuous cultivation at D = 0.025 h−1 (6.94 ± 0.27 mg/L*h−1 and 1.00 ± 0.03 mg/g*h−1, respectively). Thus, the choice of a suitable cultivation method under oxygen-limiting conditions depends heavily on the process requirements. Key points: • Measurements of respiratory activity and backscatter light of thraustochytrids • Oxygen limitation increased squalene accumulation in Schizochytrium sp. S31 • Comparison of different cultivation methods under oxygen-limiting conditions.

AB - Abstract: The triterpene squalene is widely used in the food, cosmetics and pharmaceutical industries due to its antioxidant, antistatic and anti-carcinogenic properties. It is usually obtained from the liver of deep sea sharks, which are facing extinction. Alternative production organisms are marine protists from the family Thraustochytriaceae, which produce and store large quantities of various lipids. Squalene accumulation in thraustochytrids is complex, as it is an intermediate in sterol biosynthesis. Its conversion to squalene 2,3-epoxide is the first step in sterol synthesis and is heavily oxygen dependent. Hence, the oxygen supply during cultivation was investigated in our study. In shake flask cultivations, a reduced oxygen supply led to increased squalene and decreased sterol contents and yields. Oxygen-limited conditions were applied to bioreactor scale, where squalene accumulation and growth of Schizochytrium sp. S31 was determined in batch, fed-batch and continuous cultivation. The highest dry matter (32.03 g/L) was obtained during fed-batch cultivation, whereas batch cultivation yielded the highest biomass productivity (0.2 g/L*h−1). Squalene accumulation benefited from keeping the microorganisms in the growth phase. Therefore, the highest squalene content of 39.67 ± 1.34 mg/g was achieved by continuous cultivation (D = 0.025 h−1) and the highest squalene yield of 1131 mg/L during fed-batch cultivation. Volumetric and specific squalene productivity both reached maxima in the continuous cultivation at D = 0.025 h−1 (6.94 ± 0.27 mg/L*h−1 and 1.00 ± 0.03 mg/g*h−1, respectively). Thus, the choice of a suitable cultivation method under oxygen-limiting conditions depends heavily on the process requirements. Key points: • Measurements of respiratory activity and backscatter light of thraustochytrids • Oxygen limitation increased squalene accumulation in Schizochytrium sp. S31 • Comparison of different cultivation methods under oxygen-limiting conditions.

KW - Backscatter

KW - Continuous cultivation

KW - RQ

KW - Schizochytrium sp. S31

KW - Squalene

KW - Sterols

KW - Thraustochytrids

UR - http://www.scopus.com/inward/record.url?scp=85185134550&partnerID=8YFLogxK

U2 - 10.1007/s00253-024-13051-3

DO - 10.1007/s00253-024-13051-3

M3 - Article

C2 - 38349390

AN - SCOPUS:85185134550

VL - 108

JO - Applied Microbiology and Biotechnology

JF - Applied Microbiology and Biotechnology

SN - 0175-7598

M1 - 201

ER -