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Challenges and Advances in the Bioproduction of L-Cysteine

Affiliation
Chair of Biochemical Engineering, TUM School of Engineering and Design, Technical University of Munich, Boltzmannstraße 15, D-85748 Garching, Germany;
Caballero Cerbon, Daniel Alejandro;
Affiliation
TUM School of Engineering and Design, Technical University of Munich, Boltzmannstraße 15, D-85748 Garching, Germany
Gebhard, Leon;
Affiliation
TUM Campus Straubing for Biotechnology and Sustainability, Technical University of Munich, Petersgasse 5, D-94315 Straubing, Germany;(R.D.);(T.E.);(S.H.);
Dokuyucu, Ruveyda;
Affiliation
TUM Campus Straubing for Biotechnology and Sustainability, Technical University of Munich, Petersgasse 5, D-94315 Straubing, Germany;(R.D.);(T.E.);(S.H.);
Ertl, Theresa;
Affiliation
TUM Campus Straubing for Biotechnology and Sustainability, Technical University of Munich, Petersgasse 5, D-94315 Straubing, Germany;(R.D.);(T.E.);(S.H.);
Härtl, Sophia;
Affiliation
TUM Campus Straubing for Biotechnology and Sustainability, Technical University of Munich, Petersgasse 5, D-94315 Straubing, Germany;(R.D.);(T.E.);(S.H.);
Mazhar, Ayesha;
ORCID
0000-0002-1171-4194
Affiliation
Chair of Biochemical Engineering, TUM School of Engineering and Design, Technical University of Munich, Boltzmannstraße 15, D-85748 Garching, Germany;
Weuster-Botz, Dirk

L-cysteine is a proteogenic amino acid with many applications in the pharmaceutical, food, animal feed, and cosmetic industries. Due to safety and environmental issues in extracting L-cysteine from animal hair and feathers, the fermentative production of L-cysteine offers an attractive alternative using renewable feedstocks. Strategies to improve microbial production hosts like Pantoea ananatis , Corynebacterium glutamicum , Pseudomonas sp., and Escherichia coli are summarized. Concerning the metabolic engineering strategies, the overexpression of feedback inhibition-insensitive L-serine O-acetyltransferase and weakening the degradation of L-cysteine through the removal of L-cysteine desulfhydrases are crucial adjustments. The overexpression of L-cysteine exporters is vital to overcome the toxicity caused by intracellular accumulating L-cysteine. In addition, we compiled the process engineering aspects for the bioproduction of L-cysteine. Utilizing the energy-efficient sulfur assimilation pathway via thiosulfate, fermenting cheap carbon sources, designing scalable, fed-batch processes with individual feedings of carbon and sulfur sources, and implementing efficient purification techniques are essential for the fermentative production of L-cysteine on an industrial scale.

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