Advertisement

Applied Microbiology and Biotechnology

, Volume 102, Issue 19, pp 8203–8211 | Cite as

Current understanding of sulfur assimilation metabolism to biosynthesize l-cysteine and recent progress of its fermentative overproduction in microorganisms

  • Yusuke Kawano
  • Kengo Suzuki
  • Iwao Ohtsu
Mini-Review

Abstract

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.

Keywords

l-Cysteine l-Cysteine production Sulfur assimilation Thiosulfate sulfurtransferase Escherichia coli 

Notes

Acknowledgements

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.

Funding information

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.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

References

  1. Aguilar-Barajas E, Diaz-Perez C, Ramirez-Diaz MI, Riveros-Rosas H, Cervantes C (2011) Bacterial transport of sulfate, molybdate, and related oxyanions. Biometals 24(4):687–707.  https://doi.org/10.1007/s10534-011-9421-x CrossRefPubMedGoogle Scholar
  2. Berendt U, Haverkamp T, Prior A, Schwenn JD (1995) Reaction mechanism of thioredoxin: 3′-phospho-adenylylsulfate reductase investigated by site-directed mutagenesis. Eur J Biochem 233(1):347–356.  https://doi.org/10.1111/j.1432-1033.1995.347_1.x CrossRefPubMedGoogle Scholar
  3. Boronat A, Britton P, Jones-Mortimer MC, Kornberg HL, Lee LG, Murfitt D, Parra F (1984) Location on the Escherichia coli genome of a gene specifying O-acetylserine (thiol)-lyase. J Gen Microbiol 130(3):673–685.  https://doi.org/10.1099/00221287-130-3-673 CrossRefPubMedGoogle Scholar
  4. Cheng H, Donahue JL, Battle SE, Ray WK, Larson TJ (2008) Biochemical and genetic characterization of PspE and GlpE, two single-domain Sulfurtransferases of Escherichia coli. Open Microbiol J 2:18–28.  https://doi.org/10.2174/1874285800802010018 CrossRefPubMedPubMedCentralGoogle Scholar
  5. Cherest H, Eichler F, Robichon-Szulmajster H (1969) Genetic and regulatory aspects of methionine biosynthesis in Saccharomyces cerevisiae. J Bacteriol 97(1):328–336PubMedPubMedCentralGoogle Scholar
  6. 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
  7. 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
  8. Ferla MP, Patrick WM (2014) Bacterial methionine biosynthesis. Microbiology 160(Pt 8):1571–1584.  https://doi.org/10.1099/mic.0.077826-0 CrossRefPubMedGoogle Scholar
  9. Fimmel AL, Loughlin RE (1977) Isolation and characterization of cysK mutants of Escherichia coli K12. J Gen Microbiol 103(1):37–43.  https://doi.org/10.1099/00221287-103-1-37 CrossRefPubMedGoogle Scholar
  10. 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
  11. Fujita Y, Takegawa K (2004) Characterization of two genes encoding putative cysteine synthase required for cysteine biosynthesis in Schizosaccharomyces pombe. Biosci Biotechnol Biochem 68(2):306–311.  https://doi.org/10.1271/bbb.68.306 CrossRefPubMedGoogle Scholar
  12. 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
  13. Genghof DS (1970) Biosynthesis of ergothioneine and hercynine by fungi and Actinomycetales. J Bacteriol 103(2):475–478PubMedPubMedCentralGoogle Scholar
  14. 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
  15. Hunt S (1985) Degradation of amino acids accompanying in vitro protein hydrolysis. In: Barrett GC (ed) Chemistry and biochemistry of the amino acids. Springer Netherlands, Dordrecht, pp 376–398CrossRefGoogle Scholar
  16. 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
  17. Ingenbleek Y, Kimura H (2013) Nutritional essentiality of sulfur in health and disease. Nutr Rev 71(7):413–432.  https://doi.org/10.1111/nure.12050 CrossRefPubMedGoogle Scholar
  18. Joo YC, Hyeon JE, Han SO (2017) Metabolic design of Corynebacterium glutamicum for production of l-cysteine with consideration of sulfur-supplemented animal feed. J Agric Food Chem 65(23):4698–4707.  https://doi.org/10.1021/acs.jafc.7b01061 CrossRefPubMedGoogle Scholar
  19. Kankipati HN, Rubio-Texeira M, Castermans D, Diallinas G, Thevelein JM (2015) Sul1 and Sul2 sulfate transceptors signal to protein kinase a upon exit of sulfur starvation. J Biol Chem 290(16):10430–10446.  https://doi.org/10.1074/jbc.M114.629022 CrossRefPubMedPubMedCentralGoogle Scholar
  20. Kawano Y, Ohtsu I, Takumi K, Tamakoshi A, Nonaka G, Funahashi E, Ihara M, Takagi H (2015a) Enhancement of l-cysteine production by disruption of yciW in Escherichia coli. J Biosci Bioeng 119(2):176–179.  https://doi.org/10.1016/j.jbiosc.2014.07.006 CrossRefPubMedGoogle Scholar
  21. 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
  22. 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
  23. Kerjan P, Cherest H, Surdin-Kerjan Y (1986) Nucleotide sequence of the Saccharomyces cerevisiae MET25 gene. Nucleic Acids Res 14(20):7861–7871.  https://doi.org/10.1093/nar/14.20.7861 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 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
  25. Kredich NM, Tomkins GM (1966) The enzymic synthesis of L-cysteine in Escherichia coli and Salmonella typhimurium. J Biol Chem 241(21):4955–4965PubMedGoogle Scholar
  26. Le Faou A, Rajagopal BS, Daniels L, Fauque G (1990) Thiosulfate, polythionates and elemental sulfur assimilation and reduction in the bacterial world. FEMS Microbiol Rev 6(4):351–381.  https://doi.org/10.1016/0378-1097(90)90688-M CrossRefPubMedGoogle Scholar
  27. Leyh TS, Taylor JC, Markham GD (1988) The sulfate activation locus of Escherichia coli K12: cloning, genetic, and enzymatic characterization. J Biol Chem 263(5):2409–2416PubMedGoogle Scholar
  28. Lillig CH, Prior A, Schwenn JD, Aslund F, Ritz D, Vlamis-Gardikas A, Holmgren A (1999) New thioredoxins and glutaredoxins as electron donors of 3′-phosphoadenylylsulfate reductase. J Biol Chem 274(12):7695–7698.  https://doi.org/10.1074/jbc.274.12.7695 CrossRefPubMedGoogle Scholar
  29. Liu H, Fang G, Wu H, Li Z, Ye Q (2018) L-Cysteine production in Escherichia coli based on rational metabolic engineering and modular strategy. Biotechnol J.  https://doi.org/10.1002/biot.201700695 CrossRefGoogle Scholar
  30. Maier TH (2003) Semisynthetic production of unnatural L-alpha-amino acids by metabolic engineering of the cysteine-biosynthetic pathway. Nat Biotechnol 21(4):422–427.  https://doi.org/10.1038/nbt807 CrossRefPubMedGoogle Scholar
  31. Marzluf GA (1997) Molecular genetics of sulfur assimilation in filamentous fungi and yeast. Annu Rev Microbiol 51:73–96.  https://doi.org/10.1146/annurev.micro.51.1.73 CrossRefPubMedGoogle Scholar
  32. Melideo SL, Jackson MR, Jorns MS (2014) Biosynthesis of a central intermediate in hydrogen sulfide metabolism by a novel human sulfurtransferase and its yeast ortholog. Biochemistry 53(28):4739–4753.  https://doi.org/10.1021/bi500650h CrossRefPubMedPubMedCentralGoogle Scholar
  33. 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
  34. 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
  35. Noma A, Sakaguchi Y, Suzuki T (2009) Mechanistic characterization of the sulfur-relay system for eukaryotic 2-thiouridine biogenesis at tRNA wobble positions. Nucleic Acids Res 37(4):1335–1352.  https://doi.org/10.1093/nar/gkn1023 CrossRefPubMedPubMedCentralGoogle Scholar
  36. Nonaka G, Yamazaki S, Takumi K (2012) Method for producing l-cysteine. WO patent WO 2012/137689 A1Google Scholar
  37. 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
  38. 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
  39. 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
  40. Osawa R, Kamide T, Satoh Y, Kawano Y, Ohtsu I, Dairi T (2018) Heterologous and high production of ergothioneine in Escherichia coli. J Agric Food Chem 66(5):1191–1196.  https://doi.org/10.1021/acs.jafc.7b04924 CrossRefPubMedGoogle Scholar
  41. Pfeiffer C, Bauer T, Surek B, Schomig E, Grundemann D (2011) Cyanobacteria produce high levels of ergothioneine. Food Chem 129(4):1766–1769.  https://doi.org/10.1016/j.foodchem.2011.06.047 CrossRefGoogle Scholar
  42. 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
  43. Ray WK, Zeng G, Potters MB, Mansuri AM, Larson TJ (2000) Characterization of a 12-kilodalton rhodanese encoded by glpE of Escherichia coli and its interaction with thioredoxin. J Bacteriol 182(8):2277–2284.  https://doi.org/10.1128/JB.182.8.2277-2284.2000 CrossRefPubMedPubMedCentralGoogle Scholar
  44. Ruckert C (2016) Sulfate reduction in microorganisms-recent advances and biotechnological applications. Curr Opin Microbiol 33:140–146.  https://doi.org/10.1016/j.mib.2016.07.007 CrossRefPubMedGoogle Scholar
  45. Ryu OH, Ju JY, Shin CS (1997) Continuous L-cysteine production using immobilized cell reactors and product extractors. Process Biochem 32(3):201–209.  https://doi.org/10.1016/S0032-9592(96)00061-1 CrossRefGoogle Scholar
  46. Satishchandran C, Markham GD (1989) Adenosine-5′-phosphosulfate kinase from Escherichia coli K12. Purification, characterization, and identification of a phosphorylated enzyme intermediate. J Biol Chem 264(25):15012–15021PubMedGoogle Scholar
  47. Satishchandran C, Markham GD (2000) Mechanistic studies of Escherichia coli adenosine-5′-phosphosulfate kinase. Arch Biochem Biophys 378(2):210–215.  https://doi.org/10.1006/abbi.2000.1841 CrossRefPubMedGoogle Scholar
  48. Siegel LM, Davis PS (1974) Reduced nicotinamide adenine dinucleotide phosphate-sulfite reductase of enterobacteria. IV The Escherichia coli hemoflavoprotein: subunit structure and dissociation into hemoprotein and flavoprotein components. J Biol Chem 249(5):1587–1598PubMedGoogle Scholar
  49. 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
  50. Spencer JB, Stolowich NJ, Roessner CA, Scott AI (1993) The Escherichia coli cysG gene encodes the multifunctional protein, siroheme synthase. FEBS Lett 335(1):57–60.  https://doi.org/10.1016/0014-5793(93)80438-Z CrossRefPubMedGoogle Scholar
  51. Suzuki K (2017) Large-scale cultivation of Euglena. Adv Exp Med Biol 979:285–293.  https://doi.org/10.1007/978-3-319-54910-1_14 CrossRefPubMedGoogle Scholar
  52. Takagi H, Ohtsu I (2017) L-cysteine metabolism and fermentation in microorganisms. Adv Biochem Eng Biotechnol 159:129–151.  https://doi.org/10.1007/10_2016_29 CrossRefPubMedGoogle Scholar
  53. Takumi K, Ziyatdinov MK, Samsonov V, Nonaka G (2017) Fermentative production of cysteine by Pantoea ananatis. Appl Environ Microbiol 83(5):e02502–e02516.  https://doi.org/10.1128/AEM.02502-16 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 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
  55. Thomas D, Barbey R, Henry D, Surdin-Kerjan Y (1992) Physiological analysis of mutants of Saccharomyces cerevisiae impaired in sulphate assimilation. J Gen Microbiol 138(10):2021–2028.  https://doi.org/10.1099/00221287-138-10-2021 CrossRefPubMedGoogle Scholar
  56. Thomas D, Surdin-Kerjan Y (1997) Metabolism of sulfur amino acids in Saccharomyces cerevisiae. Microbiol Mol Biol Rev 61(4):503–532PubMedPubMedCentralGoogle Scholar
  57. Toohey JI, Cooper AJ (2014) Thiosulfoxide (sulfane) sulfur: new chemistry and new regulatory roles in biology. Molecules 19(8):12789–12813.  https://doi.org/10.3390/molecules190812789 CrossRefPubMedPubMedCentralGoogle Scholar
  58. Wada M, Takagi H (2006) Metabolic pathways and biotechnological production of L-cysteine. Appl Microbiol Biotechnol 73(1):48–54.  https://doi.org/10.1007/s00253-006-0587-z CrossRefPubMedGoogle Scholar
  59. Wiriyathanawudhiwong N, Ohtsu I, Li ZD, Mori H, Takagi H (2009) The outer membrane TolC is involved in cysteine tolerance and overproduction in Escherichia coli. Appl Microbiol Biotechnol 81(5):903–913.  https://doi.org/10.1007/s00253-008-1686-9 CrossRefPubMedGoogle Scholar
  60. Yamagata S (1987) Partial purification and some properties of homoserine O-acetyltransferase of a methionine auxotroph of Saccharomyces cerevisiae. J Bacteriol 169(8):3458–3463.  https://doi.org/10.1128/jb.169.8.3458-3463.1987 CrossRefPubMedPubMedCentralGoogle Scholar
  61. 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

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Innovation Medical Research InstituteUniversity of TsukubaTsukubaJapan
  2. 2.Department of Research and DevelopmentEuglena Co., Ltd.TokyoJapan

Personalised recommendations