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l-Cysteine Metabolism Found in Saccharomyces cerevisiae and Ogataea parapolymorpha

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Non-conventional Yeasts: from Basic Research to Application

Abstract

Sulfur’s cellular requirements can be met by the cell’s uptake of sulfur-containing amino acids. The requirements can also be fulfilled by the cell’s assimilation of inorganic sulfur into organic compounds, such as l-homocysteine (Hcy) and l-cysteine (Cys), which are used for the biosynthesis of l-methionine (Met) and l-glutathione (GSH), respectively. Cys can be synthesized via the sulfur assimilation pathway in microorganisms and plants, but not the corresponding pathway in animals. Saccharomyces cerevisiae, which is the conventional yeast, synthesizes Cys from Hcy via a reverse trans-sulfuration pathway. It has been concluded that Cys is synthesized exclusively by l-cystathionine β-synthase and l-cystathionine γ-lyase. A promising host strain for high-level production of GSH is the thermotolerant methylotrophic yeast Ogataea parapolymorpha (formerly Hansenula polymorpha). Domain analyses of the serine O-acetyltransferase (SAT) in the non-conventional yeast Ogataea parapolymorpha (OpSat1) and those of other fungal SATs have demonstrated that these proteins have a mitochondrial targeting sequence (MTS) at the N-terminus that differs markedly from the classical bacterial and plant SATs. OpSat1 is functionally interchangeable with the E. coli SAT, i.e., CysE, even though compared to CysE, OpSat1 has far lower enzymatic activity, with marginal feedback inhibition by Cys. In light of the key role of OpSat1 in the regulation of the pathway of Cys biosynthesis in O. parapolymorpha, and its crucial role in sulfur metabolism, it is apparent that OpSat1 could be a target for the metabolic engineering used to generate yeast strains that produce sulfur-containing metabolites such as GSH.

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Acknowledgments

We are greatly indebted to our co-researchers Dr. Hyun Ah Kang, Ji Yoon Yeon, and Su Jin Yoo (Chung-Ang University, Seoul, Korea) and Dr. Bun-ichiro Ono (Ritsumeikan University, Japan). I am also grateful to Dr. Shigeru Nakamori (Fukui Prefectural University, Fukui, Japan) and Dr. Iwao Ohtsu (Nara Institute Science and Technology, Nara, Japan). This review includes the work supported by a grant from Ajinomoto, Co., Inc., to H.T.

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  1. Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Nara, Japan

    Hiroshi Takagi

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  1. Hiroshi Takagi
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Correspondence to Hiroshi Takagi .

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  1. Department of Molecular Genetics and Biotechnology, Institute of Cell Biology, NAS of Ukraine Lviv, Ukraine, Department of Microbiology and Biotechnology, University of Rzeszow, Rzeszow, Poland

    Andriy Sibirny

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Takagi, H. (2019). l-Cysteine Metabolism Found in Saccharomyces cerevisiae and Ogataea parapolymorpha. In: Sibirny, A. (eds) Non-conventional Yeasts: from Basic Research to Application. Springer, Cham. https://doi.org/10.1007/978-3-030-21110-3_15

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