Current understanding of sulfur assimilation metabolism to biosynthesize l-cysteine and recent progress of its fermentative overproduction in microorganisms
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To all organisms, sulfur is an essential and important element. The assimilation of inorganic sulfur molecules such as sulfate and thiosulfate into organic sulfur compounds such as l-cysteine and l-methionine (essential amino acid for human) is largely contributed by microorganisms. Of these, special attention is given to thiosulfate (S2O32−) assimilation, because thiosulfate relative to often utilized sulfate (SO42−) as a sulfur source is proposed to be more advantageous in microbial growth and biotechnological applications like l-cysteine fermentative overproduction toward industrial manufacturing. In Escherichia coli as well as other many bacteria, the thiosulfate assimilation pathway is known to depend on O-acetyl-l-serine sulfhydrylase B. Recently, another yet-unidentified CysM-independent thiosulfate pathway was found in E. coli. This pathway is expected to consist of the initial part of the thiosulfate to sulfite (SO32−) conversion, and the latter part might be shared with the final part of the known sulfate assimilation pathway [sulfite → sulfide (S2−) → l-cysteine]. The catalysis of thiosulfate to sulfite is at least partly mediated by thiosulfate sulfurtransferase (GlpE). In this mini-review, we introduce updated comprehensive information about sulfur assimilation in microorganisms, including this topic. Also, we introduce recent advances of the application study about l-cysteine overproduction, including the GlpE overexpression.
Keywordsl-Cysteine l-Cysteine production Sulfur assimilation Thiosulfate sulfurtransferase Escherichia coli
We would like to thank Taka-Aki Sato (Ph.D. Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba, Tsukuba, Japan; Shimadzu Co., Kyoto, Japan) for excellent discussion.
This review was supported in part by JSPS KAKENHI Grant Numbers JP26450091 and JP15KT0028, by Science and Technology Research Promotion Program for Agriculture, Forestry, Fisheries and Food Industry (26027AB) from MAFF, Japan, and by the grant from The SKYLARK Food Science Institute, Japan, to I.O. This work was also supported in part by JSPS KAKENHI Grant Numbers JP16K18675 and JP15KT0028 to Y.K. The funders had no role in manuscript design or the decision to submit the work for publication.
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Conflict of interest
The authors declare that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
- Cherest H, Thomas D, Surdin-Kerjan Y (1993) Cysteine biosynthesis in Saccharomyces cerevisiae occurs through the transsulfuration pathway which has been built up by enzyme recruitment. J Bacteriol 175(17):5366–5374. https://doi.org/10.1128/jb.175.17.5366-5374.1993 CrossRefPubMedPubMedCentralGoogle Scholar
- Denk D, Bock A (1987) L-cysteine biosynthesis in Escherichia coli: nucleotide sequence and expression of the serine acetyltransferase (cysE) gene from the wild-type and a cysteine-excreting mutant. J Gen Microbiol 133(3):515–525. https://doi.org/10.1099/00221287-133-3-515 CrossRefPubMedGoogle Scholar
- Franzoni F, Colognato R, Galetta F, Laurenza I, Barsotti M, Di Stefano R, Bocchetti R, Regoli F, Carpi A, Balbarini A, Migliore L, Santoro G (2006) An in vitro study on the free radical scavenging capacity of ergothioneine: comparison with reduced glutathione, uric acid and trolox. Biomed Pharmacother 60(8):453–457. https://doi.org/10.1016/j.biopha.2006.07.015 CrossRefPubMedGoogle Scholar
- Funahashi E, Saiki K, Honda K, Sugiura Y, Kawano Y, Ohtsu I, Watanabe D, Wakabayashi Y, Abe T, Nakanishi T, Suematsu M, Takagi H (2015) Finding of thiosulfate pathway for synthesis of organic sulfur compounds in Saccharomyces cerevisiae and improvement of ethanol production. J Biosci Bioeng 120:666–669. https://doi.org/10.1016/j.jbiosc.2015.04.011 CrossRefPubMedGoogle Scholar
- Holt S, Kankipati H, De Graeve S, Van Zeebroeck G, Foulquie-Moreno MR, Lindgreen S, Thevelein JM (2017) Major sulfonate transporter Soa1 in Saccharomyces cerevisiae and considerable substrate diversity in its fungal family. Nat Commun 8:14247. https://doi.org/10.1038/ncomms14247 CrossRefPubMedPubMedCentralGoogle Scholar
- Ida T, Sawa T, Ihara H, Tsuchiya Y, Watanabe Y, Kumagai Y, Suematsu M, Motohashi H, Fujii S, Matsunaga T, Yamamoto M, Ono K, Devarie-Baez NO, Xian M, Fukuto JM, Akaike T (2014) Reactive cysteine persulfides and S-polythiolation regulate oxidative stress and redox signaling. Proc Natl Acad Sci U S A 111(21):7606–7611. https://doi.org/10.1073/pnas.1321232111 CrossRefPubMedPubMedCentralGoogle Scholar
- Kawano Y, Ohtsu I, Tamakoshi A, Shiroyama M, Tsuruoka A, Saiki K, Takumi K, Nonaka G, Nakanishi T, Hishiki T, Suematsu M, Takagi H (2015b) Involvement of the yciW gene in l-cysteine and l-methionine metabolism in Escherichia coli. J Biosci Bioeng 119(3):310–313. https://doi.org/10.1016/j.jbiosc.2014.08.012 CrossRefPubMedGoogle Scholar
- Kawano Y, Onishi F, Shiroyama M, Miura M, Tanaka N, Oshiro S, Nonaka G, Nakanishi T, Ohtsu I (2017) Improved fermentative L-cysteine overproduction by enhancing a newly identified thiosulfate assimilation pathway in Escherichia coli. Appl Microbiol Biotechnol 101(18):6879–6889. https://doi.org/10.1007/s00253-017-8420-4 CrossRefPubMedGoogle Scholar
- Kredich NM (1992) The molecular basis for positive regulation of cys promoters in Salmonella typhimurium and Escherichia coli. Mol Microbiol 6(19):2747–2753. https://doi.org/10.1111/j.1365-2958.1992.tb01453.x CrossRefPubMedGoogle Scholar
- Nakano S, Ishii I, Shinmura K, Tamaki K, Hishiki T, Akahoshi N, Ida T, Nakanishi T, Kamata S, Kumagai Y, Akaike T, Fukuda K, Sano M, Suematsu M (2015) Hyperhomocysteinemia abrogates fasting-induced cardioprotection against ischemia/reperfusion by limiting bioavailability of hydrogen sulfide anions. J Mol Med (Berl) 93:879–889. https://doi.org/10.1007/s00109-015-1271-5 CrossRefGoogle Scholar
- Nakatani T, Ohtsu I, Nonaka G, Wiriyathanawudhiwong N, Morigasaki S, Takagi H (2012) Enhancement of thioredoxin/glutaredoxin-mediated L-cysteine synthesis from S-sulfocysteine increases L-cysteine production in Escherichia coli. Microb Cell Factories 11:62. https://doi.org/10.1186/1475-2859-11-62 CrossRefGoogle Scholar
- Nonaka G, Yamazaki S, Takumi K (2012) Method for producing l-cysteine. WO patent WO 2012/137689 A1Google Scholar
- Ohmura M, Hishiki T, Yamamoto T, Nakanishi T, Kubo A, Tsuchihashi K, Tamada M, Toue S, Kabe Y, Saya H, Suematsu M (2015) Impacts of CD44 knockdown in cancer cells on tumor and host metabolic systems revealed by quantitative imaging mass spectrometry. Nitric Oxide 46:102–113. https://doi.org/10.1016/j.niox.2014.11.005 CrossRefPubMedGoogle Scholar
- Ohtsu I, Kawano Y, Suzuki M, Morigasaki S, Saiki K, Yamazaki S, Nonaka G, Takagi H (2015) Uptake of L-cystine via an ABC transporter contributes defense of oxidative stress in the L-cystine export-dependent manner in Escherichia coli. PLoS One 10(3):e0120619. https://doi.org/10.1371/journal.pone.0120619 CrossRefPubMedPubMedCentralGoogle Scholar
- Ohtsu I, Wiriyathanawudhiwong N, Morigasaki S, Nakatani T, Kadokura H, Takagi H (2010) The L-cysteine/L-cystine shuttle system provides reducing equivalents to the periplasm in Escherichia coli. J Biol Chem 285(23):17479–17487. https://doi.org/10.1074/jbc.M109.081356 CrossRefPubMedPubMedCentralGoogle Scholar
- Pluskal T, Ueno M, Yanagida M (2014) Genetic and metabolomic dissection of the ergothioneine and selenoneine biosynthetic pathway in the fission yeast, S. pombe, and construction of an overproduction system. PLoS One 9(5):e97774. https://doi.org/10.1371/journal.pone.0097774 CrossRefPubMedPubMedCentralGoogle Scholar
- Sirko A, Zatyka M, Sadowy E, Hulanicka D (1995) Sulfate and thiosulfate transport in Escherichia coli K-12: evidence for a functional overlapping of sulfate- and thiosulfate-binding proteins. J Bacteriol 177(14):4134–4136. https://doi.org/10.1128/jb.177.14.4134-4136.1995 CrossRefPubMedPubMedCentralGoogle Scholar
- Tamura Y, Nishino M, Ohmachi T, Asada Y (1998) N-Carbamoyl-L-Cysteine as an Intermediate in the bioconversion from D,L-2-Amino-Delta (2)-Thiazoline-4-Carboxylic Acid to L-Cysteine by Pseudomonas sp. ON-4a. Biosci Biotechnol Biochem 62(11):2226–2229. https://doi.org/10.1271/bbb.62.2226 CrossRefPubMedGoogle Scholar
- Yamagata S, Takeshima K, Naiki N (1974) Evidence for the identity of O-acetylserine sulfhydrylase with O-acetylhomoserine sulfhydrylase in yeast. J Biochem 75(6):1221–1229. https://doi.org/10.1093/oxfordjournals.jbchem.a130505 CrossRefPubMedGoogle Scholar