Physcomitrella patens, a versatile synthetic biology chassis



Key message

During three decades the moss Physcomitrella patens has been developed to a superb green cell factory with the first commercial products on the market.


In the past three decades the moss P. patens has been developed from an obscure bryophyte to a model organism in basic biology, biotechnology, and synthetic biology. Some of the key features of this system include a wide range of Omics technologies, precise genome-engineering via homologous recombination with yeast-like efficiency, a certified good-manufacturing-practice production in bioreactors, successful upscaling to 500 L wave reactors, excellent homogeneity of protein products, superb product stability from batch-to-batch, and a reliable procedure for cryopreservation of cell lines in a master cell bank. About a dozen human proteins are being produced in P. patens as potential biopharmaceuticals, some of them are not only similar to their animal-produced counterparts, but are real biobetters with superior performance. A moss-made pharmaceutical successfully passed phase 1 clinical trials, a fragrant moss, and a cosmetic moss-product is already on the market, highlighting the economic potential of this synthetic biology chassis. Here, we focus on the features of mosses as versatile cell factories for synthetic biology and their impact on metabolic engineering.


Biopharmaceutical Bioreactor Fragrance Gene targeting Genome engineering Green cell factory Photobioreactor 



Work in our laboratories is funded by the Marie Curie Actions of the European Union’s Horizon 2020 (Grant agreement no. 765115 MossTech to H. T. S., H. B. and R. R.), the Excellence Initiative of the German Federal and State Governments (EXC 294 to R. R.) and The Danish Council for Independent Research (#4005-00158B to H. T. S. and H. B.).

Compliance with ethical standards

Conflict of interest

R. R. is an inventor of the moss bioreactor and a founder of Greenovation Biotech GmbH. He currently serves as advisory board member of this company. H. T. S. is the co-founder and CEO of Mosspiration Biotech IVS along with H. B. who is the co-founder and CSO of this company. All authors are inventors of patents and patent applications related to the topics discussed here. The Chair of Plant Biotechnology at the University of Freiburg, headed by R. R., developed and hosts the resources and


  1. Anterola A, Shanle E, Perroud P-F, Quatrano R (2009) Production of taxa-4(5),11(12)-diene by transgenic Physcomitrella patens. Transg Res 18:655–660CrossRefGoogle Scholar
  2. Asakawa Y (1995) Chemical constituents of the bryophytes. In: Progress in the chemistry of organic natural products. Fortschritte der Chemie organischer Naturstoffe, vol 65. Springer, Vienna, pp 1–565Google Scholar
  3. Bach SS, King BC, Zhan X, Simonsen HT, Hamberger B (2014) Heterologous stable expression of terpenoid biosynthetic genes using the moss Physcomitrella patens. In: Rodríguez-Concepción M (ed) Plant isoprenoids. Springer, New York, pp 257–271CrossRefGoogle Scholar
  4. Baird RD, Tan DSP, Kaye SB (2010) Weekly paclitaxel in the treatment of recurrent ovarian cancer. Nat Rev Clin Oncol 7:575–582PubMedCrossRefGoogle Scholar
  5. Baldovini N, Delasalle C, Joulain D (2011) Phytochemistry of the heartwood from fragrant Santalum species: a review. Flavour Fragr J 26:7–26CrossRefGoogle Scholar
  6. Baur A, Reski R, Gorr G (2005a) Enhanced recovery of a secreted recombinant human growth factor using stabilizing additives and by co-expression of human serum albumin in the moss Physcomitrella patens. Plant Biotechnol J 3:331–340PubMedCrossRefGoogle Scholar
  7. Baur A, Kaufmann F, Rolli H, Weise A, Luethje R, Berg B, Braun M, Baeumer W, Kietzmann M, Reski R, Gorr G (2005b) A fast and flexible PEG-mediated transient expression system in plants for high level expression of secreted recombinant proteins. J Biotechnol 119:332–342PubMedCrossRefGoogle Scholar
  8. Beike AK, Jaeger C, Zink F, Decker EL, Reski R (2014) High contents of very long chain polyunsaturated fatty acids in different moss species. Plant Cell Rep 33:245–254PubMedCrossRefGoogle Scholar
  9. Beike AK, Spagnuolo V, Lüth V, Steinhart F, Ramos-Gomez J, Krebs M, Adamo P, Rey-Asensio AI, Fernandez JA, Giordano S, Decker EL, Reski R (2015a) Clonal in vitro propagation of peat mosses (Sphagnum L.) as novel green resources for basic and applied research. Plant Cell Tissue Org Cult 120:1037–1049CrossRefGoogle Scholar
  10. Beike AK, Lang D, Zimmer AD, Wüst F, Trautmann D, Wiedemann G, Beyer P, Decker EL, Reski R (2015b) Insights from the cold transcriptome of Physcomitrella patens: global specialization pattern of conserved transcriptional regulators and identification of orphan genes involved in cold acclimation. New Phytol 205:869–881PubMedCrossRefGoogle Scholar
  11. Büttner-Mainik A, Parsons J, Jérôme H, Hartmann A, Lamer S, Schaaf A, Schlosser A, Zipfel PF, Reski R, Decker EL (2011) Production of biologically active recombinant human factor H in Physcomitrella. Plant Biotechnol J 9:373–383PubMedCrossRefGoogle Scholar
  12. Cerff M, Posten C (2012) Enhancing the growth of Physcomitrella patens by combination of monochromatic red and blue light—a kinetic study. Biotechnol J 7:527–526PubMedCrossRefGoogle Scholar
  13. Cross LL, Paudyal R, Kamisugi Y, Berry A, Cuming AC, Baker A, Warriner SL (2017) Towards designer organelles by subverting the peroxisomal import pathway. Nat Commun 8:454PubMedPubMedCentralCrossRefGoogle Scholar
  14. Decker EL, Reski R (2007) Moss bioreactors producing improved biopharmaceuticals. Curr Op Biotechnol 18:393–398CrossRefGoogle Scholar
  15. Decker EL, Wiedemann G, Reski R (2015) Gene targeting for precision glyco-engineering: production of biopharmaceuticals devoid of plant-typical glycosylation in moss bioreactors. Methods Mol Biol 1321:213–224PubMedCrossRefGoogle Scholar
  16. Egener T, Granado J, Guitton MC, Hohe A, Holtorf H, Lucht JM, Rensing SA, Schlink K, Schulte J, Schween G, Zimmermann S, Duwenig E, Rak B, Reski R (2002) High frequency of phenotypic deviations in Physcomitrella patens plants transformed with a gene-disruption library. BMC Plant Biol 2:6PubMedPubMedCentralCrossRefGoogle Scholar
  17. Faraldos JA, Wu S, Chappell J, Coates RM (2010) Doubly deuterium-labeled patchouli alcohol from cyclization of singly labeled [2-2H1]farnesyl diphosphate catalyzed by recombinant patchoulol synthase. J Am Chem Soc 132:2998–3008PubMedCrossRefGoogle Scholar
  18. Gibson DG (2009) Synthesis of DNA fragments in yeast by one-step assembly of overlapping oligonucleotides. Nucl Acids Res 37:6984–6990PubMedPubMedCentralCrossRefGoogle Scholar
  19. Gibson DG, Benders GA, Axelrod KC, Zaveri J, Algire MA, Moodie M, Montague MG, Venter JC, Smith HO, Hutchison CA (2008) One-step assembly in yeast of 25 overlapping DNA fragments to form a complete synthetic Mycoplasma genitalium genome. Proc Natl Acad Sci USA 105:20404–20409PubMedPubMedCentralCrossRefGoogle Scholar
  20. Giri A, Narasu ML (2000) Transgenic hairy roots: recent trends and applications. Biotechnol Adv 18:1–22PubMedCrossRefGoogle Scholar
  21. Girke T, Schmidt H, Zähringer U, Reski R, Heinz E (1998) Identification of a novel Delta 6-acyl-group desaturase by targeted gene disruption in Physcomitrella patens. Plant J 15:39–48PubMedCrossRefGoogle Scholar
  22. Gitzinger M, Parsons J, Reski R, Fussenegger M (2009) Functional cross-kingdom conservation of mammalian and moss (Physcomitrella patens) transcription, translation and secretion machineries. Plant Biotechnol J 7:73–86PubMedCrossRefGoogle Scholar
  23. Goel HL, Mercurio AM (2013) VEGF targets the tumour cell. Nat Rev Cancer 13:871–882PubMedPubMedCentralCrossRefGoogle Scholar
  24. Gorr G, Decker E, Kietzmann M, Reski R (2001) Using a moss for the expression of recombinant human vascular endothelial growth factor: an alternative system for the production of biotech pharmaceuticals. Naunyn-Schmiedebergs Arch Pharmacol 363:R86Google Scholar
  25. Häffner K, Parsons J, Bohlender LL, Hoernstein S, Niederkrüger H, Fode B, Busch A, Krieghoff N, Koch J, Schaaf A, Frischmuth T, Zipfel PF, Pohl M, Reski R, Decker EL, Michelfelder S (2017) Treatment of experimental C3 Glomerulopathy by human complement factor H produced in glycosylation-optimized Physcomitrella patens. Mol Immunol 89:120CrossRefGoogle Scholar
  26. Hayashi K-I, Horie K, Hiwatashi Y, Kawaide H, Yamaguchi S, Hanada A, Nakashima T, Nakajima M, Mander LN, Yamane H, Hasebe M, Nozaki H (2010) Endogenous diterpenes derived from ent-kaurene, a common gibberellin precursor, regulate protonema differentiation of the moss Physcomitrella patens. Plant Physiol 153:1085–1097PubMedPubMedCentralCrossRefGoogle Scholar
  27. Hebecker M, Alba-Domínguez M, Roumenina LT, Reuter S, Hyvärinen S, Dragon-Durey M-A, Jokiranta TS, Sánchez-Corral P, Józsi M (2013) An engineered construct combining complement regulatory and surface-recognition domains represents a minimal-size functional Factor H. J Immunol 191:912–921PubMedCrossRefGoogle Scholar
  28. Heinz E, Girke T, Scheffler J, Da Costa e Silva O, Schmidt H, Zähringer U, Reski R (2017) Plants expressing Delta 6-desaturase genes and oils from these plants containing PUFAS and method for producing unsaturated fatty acids. Patent US 09611441Google Scholar
  29. Henes B, Zülli F, Niederkrüger H, Schaaf A, Frischmuth T, Decker EL, Reski R (2018) The magic of moss. Soap Perfum Cosmet 91:64–66Google Scholar
  30. Henriques de Jesus MPR, Zygaldo Nielsen A, Busck Mellor S, Matthes A, Burow M, Robinson C, Erik Jensen P (2017) Tat proteins as novel thylakoid membrane anchors organize a biosynthetic pathway in chloroplasts and increase product yield 5-fold. Metab Eng 44:108–116PubMedCrossRefGoogle Scholar
  31. Hirano K, Nakajima M, Asano K, Nishiyama T, Sakakibara H, Kojima M, Katoh E, Xiang H, Tanahashi T, Hasebe M, Banks JA, Ashikari M, Kitano H, Ueguchi-Tanaka M, Matsuoka M (2007) The GID1-mediated gibberellin perception mechanism is conserved in the lycophyte Selaginella moellendorffii but not in the bryophyte Physcomitrella patens. Plant Cell 19:3058–3079PubMedPubMedCentralCrossRefGoogle Scholar
  32. Hiss M, Laule O, Meskauskiene RM, Arif MA, Decker EL, Erxleben A, Frank W, Hanke ST, Lang D, Martin A, Neu C, Reski R, Richardt S, Schallenberg-Rüdinger M, Szövényi P, Tiko T, Wiedemann G, Wolf L, Zimmermann P, Rensing SA (2014) Large-scale gene expression profiling data for the model moss Physcomitrella patens aid understanding of developmental progression, culture and stress conditions. Plant J 79:530–539PubMedCrossRefGoogle Scholar
  33. Hohe A, Reski R (2002) Optimisation of a bioreactor culture of the moss Physcomitrella patens for mass production of protoplasts. Plant Sci 163:69–74CrossRefGoogle Scholar
  34. Hohe A, Reski R (2005) From axenic spore germination to molecular farming: one century of bryophyte in vitro culture. Plant Cell Rep 23:513–521PubMedCrossRefGoogle Scholar
  35. Hohe A, Decker EL, Gorr G, Schween G, Reski R (2002a) Tight control of growth and cell differentiation in photoautotrophically growing moss (Physcomitrella patens) bioreactor cultures. Plant Cell Rep 20:1135–1140CrossRefGoogle Scholar
  36. Hohe A, Rensing SA, Mildner M, Lang D, Reski R (2002b) Day length and temperature strongly influence sexual reproduction and expression of a novel MADS-box gene in the moss Physcomitrella patens. Plant Biol 4:595–602CrossRefGoogle Scholar
  37. Hohe A, Egener T, Lucht JM, Holtorf H, Reinhard C, Schween G, Reski R (2004) An improved and highly standardised transformation procedure allows efficient production of single and multiple targeted gene-knockouts in a moss, Physcomitrella patens. Curr Genet 44:339–347PubMedCrossRefGoogle Scholar
  38. Holtorf H, Hohe A, Wang HL, Jugold M, Rausch T, Duwenig E, Reski R (2002) Promoter subfragments of the sugar beet V-type H+-ATPase subunit c isoform drive the expression of transgenes in the moss Physcomitrella patens. Plant Cell Rep 21:341–346CrossRefGoogle Scholar
  39. Horst NA, Reski R (2016) Alternation of generations—unravelling the underlying molecular mechanism of a 165-year old botanical observation. Plant Biol 18:549–551PubMedCrossRefGoogle Scholar
  40. Horstmann V, Huether CM, Jost W, Reski R, Decker EL (2004) Quantitative promoter analysis in Physcomitrella patens: a set of plant vectors activating gene expression within three orders of magnitude. BMC Biotechnol 4:13PubMedPubMedCentralCrossRefGoogle Scholar
  41. Huether CM, Lienhart O, Baur A, Stemmer C, Gorr G, Reski R, Decker EL (2005) Glyco-engineering of moss lacking plant-specific sugar residues. Plant Biol 7:292–299PubMedCrossRefGoogle Scholar
  42. Ikram NKBK, Simonsen HT (2017) A review of biotechnological artemisinin production in plants. Front Plant Sci 8:1966PubMedPubMedCentralCrossRefGoogle Scholar
  43. Ikram NKBK, Zhan X, Pan X, King BC, Simonsen HT (2015) Stable heterologous expression of biologically active terpenoids in green plant cells. Front Plant Sci 6:129PubMedPubMedCentralCrossRefGoogle Scholar
  44. Jones CG, Moniodis J, Zulak KG, Scaffidi A, Plummer JA, Ghisalberti EL, Barbour EL, Bohlmann J (2011) Sandalwood fragrance biosynthesis involves sesquiterpene synthases of both the terpene synthase (TPS)-a and TPS-b subfamilies, including santalene synthases. J Biol Chem 286:17445–17454PubMedPubMedCentralCrossRefGoogle Scholar
  45. Jost W, Link S, Horstmann V, Decker EL, Reski R, Gorr G (2005) Isolation and characterisation of three moss-derived beta-tubulin promoters suitable for recombinant expression. Curr Genet 47:111–120PubMedCrossRefGoogle Scholar
  46. Kamisugi Y, Schlink K, Rensing SA, Schween G, Stackelberg M von, Cuming AC, Reski R, Cove DJ (2006) The mechanism of gene targeting in Physcomitrella patens: homologous recombination, concatenation and multiple integration. Nucl Acids Res 34:6205–6214PubMedPubMedCentralCrossRefGoogle Scholar
  47. Kammerer W, Cove DJ (1996) Genetic analysis of the effects of re-transformation of transgenic lines of the moss Physcomitrella patens. Mol Gen Genet 250:380–382PubMedGoogle Scholar
  48. Khairul Ikram NKB, Beyraghdar Kashkooli A, Peramuna AV, van der Krol AR, Bouwmeester H, Simonsen HT (2017) Stable production of the antimalarial drug artemisinin in the moss Physcomitrella patens. Front Bioeng Biotechnol 5:47PubMedPubMedCentralCrossRefGoogle Scholar
  49. Khraiwesh B, Ossowski S, Weigel D, Reski R, Frank W (2008) Specific gene silencing by artificial microRNAs in Physcomitrella patens: an alternative to targeted gene knockouts. Plant Physiol 148:684–693PubMedPubMedCentralCrossRefGoogle Scholar
  50. Khraiwesh B, Arif MA, Seumel GI, Ossowski S, Weigel D, Reski R, Frank W (2010) Transcriptional control of gene expression by microRNAs. Cell 140:111–122PubMedCrossRefGoogle Scholar
  51. Kieran PM, MacLoughlin PF, Malone DM (1997) Plant cell suspension cultures: some engineering considerations. J Biotechnol 59:39–52PubMedCrossRefGoogle Scholar
  52. King BC, Vavitsas K, Ikram NK, Schrøder J, Scharff LB, Hamberger B, Jensen PE, Simonsen HT (2016) In vivo assembly of DNA-fragments in the moss, Physcomitrella patens. Sci Rep 6:25030PubMedPubMedCentralCrossRefGoogle Scholar
  53. Koprivova A, Stemmer C, Altmann F, Hoffmann A, Kopriva S, Gorr G, Reski R, Decker EL (2004) Targeted knockouts of Physcomitrella lacking plant-specific immunogenic N-glycans. Plant Biotechnol J 2:517–523PubMedCrossRefGoogle Scholar
  54. Kubo M, Imai A, Nishiyama T, Ishikawa M, Sato Y, Kurata T, Hiwatashi Y, Reski R, Hasebe M (2013) System for stable β-estradiol-inducible gene expression in the moss Physcomitrella patens. PLoS ONE 8:e77356PubMedPubMedCentralCrossRefGoogle Scholar
  55. Kumar S, Hahn FM, Baidoo E, Kahlon TS, Wood DF, McMahan CM, Cornish K, Keasling JD, Daniell H, Whalen MC (2012) Remodeling the isoprenoid pathway in tobacco by expressing the cytoplasmic mevalonate. Metab Eng 14:19–28PubMedCrossRefGoogle Scholar
  56. Lang D, Zimmer AD, Rensing SA, Reski R (2008) Exploring plant biodiversity: the Physcomitrella genome and beyond. Trends Plant Sci 13:542–549PubMedCrossRefGoogle Scholar
  57. Lang D, Ullrich KK, Murat F, Fuchs J, Jenkins J, Haas FB, Piednoel M, Gundlach H, Van Bel M, Meyberg R, Vives C, Morata J, Symeonidi A, Hiss M, Muchero W, Kamisugi Y, Saleh O, Blanc G, Decker EL, van Gessel N, Grimwood J, Hayes RD, Graham SW, Gunter LE, McDaniel S, Hoernstein SNW, Larsson A, Li J, Phillips F-W, Ranjan P, Rokshar DS, Rothfels CJ, Schneider L, Shu S, Stevenson DW, Thümmler F, Tillich M, Villarreal JC, Widiez T, Wong GK-S, Wymore A, Zhang Y, Zimmer AD, Quatrano RS, Mayer KFX, Goodstein D, Casacuberta JM, Vandepoele K, Reski R, Cuming AC, Tuskan J, Maumus F, Salse J, Schmutz J, Rensing SA (2018) The Physcomitrella patens chromosome-scale assembly reveals moss genome structure and evolution. Plant J 93:515–533PubMedCrossRefGoogle Scholar
  58. Larkin PJ, Scowcroft WR (1981) Somaclonal variation—a novel source of variability from cell cultures for plant improvement. Theor Appl Genet 60:197–214PubMedCrossRefGoogle Scholar
  59. Lopez-Obando M, Hoffmann B, Géry C, Guyon-Debast A, Téoulé E, Rameau C, Bonhomme S, Nogué F (2016) Simple and efficient targeting of multiple genes through CRISPR-Cas9 in Physcomitrella patens. G3 (Bethesda) 6:3647–3653Google Scholar
  60. Michelfelder S, Parsons J, Bohlender LL, Hoernstein SNW, Niederkrüger H, Busch A, Krieghoff N, Koch J, Fode B, Schaaf A, Frischmuth T, Pohl M, Zipfel PF, Reski R, Decker EL, Häffner K (2017) Moss-produced, glycosylation-optimized human factor H for therapeutic application in complement disorders. J Am Soc Nephrol 28:1462–1474PubMedCrossRefGoogle Scholar
  61. Michelfelder S, Fischer F, Wäldin A, Hörle KV, Pohl M, Parsons J, Reski R, Decker EL, Zipfel PF, Skerka C, Häffner K (2018) The MFHR1 fusion protein is a novel synthetic multitarget complement inhibitor with therapeutic potential. J Am Soc Nephrol 29:1141–1153PubMedCrossRefGoogle Scholar
  62. Morath V, Truong D-JJ, Albrecht F, Polte I, Ciccone RA, Funke LF, Reichart L, Wolf CG, Brunner A-D, Fischer K, Schneider PC, Brüggenthies JB, Fröhlich F, Wiedemann G, Reski R, Skerra A (2014) Design and characterization of a modular membrane protein anchor to functionalize the moss Physcomitrella patens with extracellular catalytic and/or binding activities. ACS Synth Biol 3:990–994PubMedCrossRefGoogle Scholar
  63. Mosquna A, Katz A, Decker EL, Rensing SA, Reski R, Ohad N (2009) Regulation of stem cell maintenance by the Polycomb protein FIE has been conserved during land plant evolution. Development 136:2433–2444PubMedCrossRefGoogle Scholar
  64. Mueller SJ, Lang D, Hoernstein SNW, Lang EGE, Schuessele C, Schmidt A, Fluck M, Leisibach D, Niegl C, Zimmer AD, Schlosser A, Reski R (2014) Quantitative analysis of the mitochondrial and plastid proteomes of the moss Physcomitrella patens reveals protein macrocompartmentation and microcompartmentation. Plant Physiol 164:2081–2095PubMedPubMedCentralCrossRefGoogle Scholar
  65. Müller K, Siegel D, Jahnke FR, Gerrer K, Wend S, Decker EL, Reski R, Weber W, Zurbriggen MD (2014) A red light-controlled synthetic gene expression switch for plant systems. Mol Biosyst 10:1679–1688PubMedCrossRefGoogle Scholar
  66. Muren E, Nilsson A, Ulfstedt M, Johansson M, Ronne H (2017) Rescue and characterization of episomally replicating DNA from the moss Physcomitrella. Proc Natl Acad Sci USA 106:19444–19449CrossRefGoogle Scholar
  67. Niederkrüger H, Dabrowska-Schlepp P, Schaaf A (2014) Suspension culture of plant cells under phototrophic conditions. In: Meyer H-P, Schmidhalter DR (eds) Industrial scale suspension culture of living cells. Wiley, Oxford, pp 259–292Google Scholar
  68. Orellana-Escobedo L, Rosales-Mendoza S, Romero-Maldonado A, Parsons J, Decker EL, Monreal-Escalante E, Moreno-Fierros L, Reski R (2015) An Env-derived multi-epitope HIV chimeric protein produced in the moss Physcomitrella patens is immunogenic in mice. Plant Cell Rep 34:425–433PubMedCrossRefGoogle Scholar
  69. Ortiz-Ramirez C, Hernandez-Coronado M, Thamm A, Catarino B, Wang MY, Dolan L, Feijo JA, Becker JD (2016) A transcriptome atlas of Physcomitrella patens provides insights into the evolution and development of land plants. Mol Plant 9:205–220PubMedCrossRefGoogle Scholar
  70. Pan X-W, Han L, Zhang Y-H, Chen D-F, Simonsen HT (2015) Sclareol production in the moss Physcomitrella patens and observations on growth and terpenoid biosynthesis. Plant Biotechnol Rep 9:149–159CrossRefGoogle Scholar
  71. Peramuna A, Bae H, Rasmussen EK, Dueholm B, Waibel T, Critchley JH, Brzezek K, Roberts M, Simonsen HT (2018a) Evaluation of synthetic promoters in Physcomitrella patens. Biochem Biophys Res Comm. PubMedCrossRefGoogle Scholar
  72. Peramuna A, Bae H, Rasmussen EK, López CQ, Fromberg A, Simonsen HT (2018b) Attaching patchoulol synthase to lipid droplet-associated proteins increase the level of patchoulol in the lipid droplets. Plant Biotechnol J (in press) Google Scholar
  73. Perner-Nochta I, Lucumi A, Posten C (2007) Photoautotrophic cell and tissue culture in a tubular photobioreactor. Eng Life Sci 7:127–135CrossRefGoogle Scholar
  74. Perroud PF, Haas FB, Hiss M, Ullrich KK, Alboresi A, Amirebrahimi M, Barry K, Bassi R, Bonhomme S, Chen H, Coates J, Fujita T, Guyon-Debast A, Lang D, Lin J, Lipzen A, Nogue F, Oliver MJ, Ponce de Léon I, Quatrano RS, Rameau C, Reiss B, Reski R, Ricca M, Saidi Y, Sun N, Szövenyi P, Sreedasyam A, Grimwood J, Stacey G, Schmutz J, Rensing SA (2018) The Physcomitrella patens gene atlas project: large scale RNA-seq based expression data. Plant J. CrossRefPubMedGoogle Scholar
  75. Phillips RL, Kaeppler SM, Olhoft P (1994) Genetic instability of plant tissue cultures: breakdown of normal controls. Proc Natl Acad Sci USA 91:5222–5226PubMedPubMedCentralCrossRefGoogle Scholar
  76. Puttick MN, Morris JL, Willimas TA, Cox CJ, Edwards D, Kenrick P, Pressel S, Wellman CH, Schneider H, Pisani D, Donoghue PCJ (2018) The interrelationship of land plants and the nature of the ancestral embryophyte. Curr Biol 28:733–745PubMedCrossRefGoogle Scholar
  77. Renault H, Alber A, Horst NA, Lopes AB, Fich EA, Kriegshauser L, Wiedemann G, Ullmann P, Herrgott L, Erhardt M, Pineau E, Ehlting J, Schmitt M, Rose JKC, Reski R, Werck-Reichhart D (2017) A phenol-enriched cuticle is ancestral to lignin evolution in land plants. Nat Commun 8:14713PubMedPubMedCentralCrossRefGoogle Scholar
  78. Rensing SA, Ick J, Fawcett JA, Lang D, Zimmer A, Van de Peer Y, Reski R (2007) An ancient genome duplication contributed to the abundance of metabolic genes in the moss Physcomitrella patens. BMC Evol Biol 7:130PubMedPubMedCentralCrossRefGoogle Scholar
  79. Rensing SA, Lang D, Zimmer AD, Terry A, Salamov A, Shapiro H, Nishiyama T, Perroud P-F, Lindquist EA, Kamisugi Y, Tanahash T, Sakakibara K, Fujita T, Oishi K, Shin-I T, Kuroki Y, Toyoda A, Suzuki Y, Hashimoto S-i, Yamaguchi K, Sugano S, Kohara Y, Fujiyama A, Ashton N, Anterola A, Aoki S, Barbazuk WB, Barker E, Bennetzen J, Blankenship R, Cho SH, Dutcher S, Estelle M, Fawcett JA, Gundlach H, Hanada K, Heyl A, Hicks KA, Hughes J, Lohr M, Mayer K, Melkozernov A, Murata T, Nelson D, Pils B, Prigge M, Reiss B, Renner T, Rombauts S, Rushton P, Sanderfoot A, Schween G, Shiu S-H, Stueber K, Theodoulou FL, Tu H, Van de Peer Y, Verrier PJ, Waters E, Wood A, Yang L, Cove D, Cuming AC, Hasebe M, Lucas S, Mishler BD, Reski R, Grigoriev I, Quatrano RS, Boore JL (2008) The Physcomitrella genome reveals evolutionary insights into the conquest of land by plants. Science 319:64–69PubMedCrossRefGoogle Scholar
  80. Reski R (1998a) Development, genetics and molecular biology of mosses. Bot Acta 111:1–15CrossRefGoogle Scholar
  81. Reski R (1998b) Physcomitrella and Arabidopsis: the David and Goliath of reverse genetics. Trends Plant Sci 3:209–210CrossRefGoogle Scholar
  82. Reski R (2018) Enabling the water-to-land transition. Nat Plants 4:67–68PubMedCrossRefGoogle Scholar
  83. Reski R, Frank W (2005) Moss (Physcomitrella patens) functional genomics—gene discovery and tool development, with implications for crop plants and human health. Brief Funct Genom Proteom 4:48–57CrossRefGoogle Scholar
  84. Reski R, Faust M, Wang XH, Wehe M, Abel WO (1994) Genome analysis of the moss Physcomitrella patens (Hedw) B.S.G. Mol Gen Genet 244:352–359PubMedCrossRefGoogle Scholar
  85. Reski R, Parsons J, Decker EL (2015) Moss-made pharmaceuticals: from bench to bedside. Plant Biotechnol J 13:1191–1198PubMedPubMedCentralCrossRefGoogle Scholar
  86. Reutter K, Reski R (1996) Production of a heterologous protein in bioreactor cultures of fully differentiated moss plants. Plant Tissue Cult Biotechnol 2:142–147Google Scholar
  87. Reutter K, Atzorn R, Hadeler B, Schmülling T, Reski R (1998) Expression of the bacterial ipt gene in Physcomitrella rescues mutations in budding and in plastid division. Planta 206:196–203CrossRefGoogle Scholar
  88. Richardt S, Timmerhaus G, Lang D, Qudeimat E, Corrêa LGG, Reski R, Rensing SA, Frank W (2010) Microarray analysis of the moss Physcomitrella patens reveals evolutionarily conserved transcriptional regulation of salt stress and abscisic acid signalling. Plant Mol Biol 72:27–45PubMedCrossRefGoogle Scholar
  89. Rosales-Mendoza S, Orellana-Escobedo L, Romero-Maldonado A, Decker EL, Reski R (2014) The potential of Physcomitrella patens as a platform for the production of plant-based vaccines. Expert Rev Vaccines 13:203–212PubMedCrossRefGoogle Scholar
  90. Roskoski R Jr (2007) Vascular endothelial growth factor (VEGF) signaling in tumor progression. Crit Rev Oncol Hematol 62:179–213PubMedCrossRefGoogle Scholar
  91. Sabovljević MS, Sabovljević AD, Ikram NKK, Peramuna A, Bae H, Simonsen HT (2016) Bryophytes—an emerging source for herbal remedies and chemical production. Plant Genet Resour 14:314–327CrossRefGoogle Scholar
  92. Saidi Y, Finka A, Chakhporanian M, Zrÿd J-P, Schaefer DG, Goloubinoff P (2005) Controlled expression of recombinant proteins in Physcomitrella patens by a conditional heat-shock promoter: a tool for plant research and biotechnology. Plant Mol Biol 59:697–711PubMedCrossRefGoogle Scholar
  93. Schaaf A, Tintelnot S, Baur A, Reski R, Gorr G, Decker EL (2005) Use of endogenous signal sequences for transient production and efficient secretion by moss (Physcomitrella patens) cells. BMC Biotechnol 5:30PubMedPubMedCentralCrossRefGoogle Scholar
  94. Schaefer DG, Zrÿd J-P (1997) Efficient gene targeting in the moss Physcomitrella patens. Plant J 11:1195–1206PubMedCrossRefGoogle Scholar
  95. Schaefer DG, Zrÿd J-P (2001) The moss Physcomitrella patens, now and then. Plant Physiol 127:1430–1438PubMedPubMedCentralCrossRefGoogle Scholar
  96. Schaefer D, Zrÿd J-P, Knight CD, Cove DJ (1991) Stable transformation of the moss Physcomitrella patens. Mol Gen Genet 226:418–424PubMedCrossRefGoogle Scholar
  97. Schmidtko J, Peine S, El-Housseini Y, Pascual M, Meier P (2013) Treatment of atypical hemolytic uremic syndrome and thrombotic microangiopathies: a focus on Eculizumab. Am J Kidney Dis 61:289–299PubMedCrossRefGoogle Scholar
  98. Schulte J, Reski R (2004) High throughput cryopreservation of 140,000 Physcomitrella patens mutants. Plant Biol 6:119–127PubMedCrossRefGoogle Scholar
  99. Schween G, Hohe A, Koprivova A, Reski R (2003) Effects of nutrients, cell density and culture techniques on protoplast regeneration and early protonema development in a moss, Physcomitrella patens. J Plant Physiol 160:209–212PubMedCrossRefGoogle Scholar
  100. Schween G, Egener T, Fritzowsky D, Granado J, Guitton MC, Hartmann N, Hohe A, Holtorf H, Lang D, Lucht JM, Reinhard C, Rensing SA, Schlink K, Schulte J, Reski R (2005) Large-scale analysis of 73,329 Physcomitrella plants transformed with different gene disruption libraries: production parameters and mutant phenotypes. Plant Biol 7:228–237PubMedCrossRefGoogle Scholar
  101. Shen JS, Busch A, Day TS, Meng XL, Yu CI, Dabrowska-Schlepp P, Fode B, Niederkrüger H, Forni S, Chen SY, Schiffmann R, Frischmuth T, Schaaf A (2016) Mannose receptor-mediated delivery of moss-made alpha galactosidase A efficiently corrects deficiency in Fabry mice. J Inherit Metabol Dis 39:293–303CrossRefGoogle Scholar
  102. Simonsen HT, Drew DP, Lunde C (2009) Perspectives on using Physcomitrella patens as an alternative production platform for thapsigargin and other terpenoid drug candidates. Perspect Med Chem 3:1–6Google Scholar
  103. Strepp R, Scholz S, Kruse S, Speth V, Reski R (1998) Plant nuclear gene knockout reveals a role in plastid division for the homolog of the bacterial cell division protein FtsZ, an ancestral tubulin. Proc Natl Acad Sci USA 95:4368–4373PubMedPubMedCentralCrossRefGoogle Scholar
  104. Ulfstedt M, Hu GZ, Johansson M, Ronne H (2017) Testing of auxotrophic selection markers for use in the moss Physcomitrella provides new insights into the mechanisms of targeted recombination. Front Plant Sci 8:1850PubMedPubMedCentralCrossRefGoogle Scholar
  105. Vesty EF, Saidi Y, Moody LA, Holloway D, Whitbread A, Needs S, Choudhary A, Burns B, Mcleod D, Bradshaw SJ, Bae H, King BC, Bassel GW, Simonsen HT, Coates JC (2016) The decision to germinate is regulated by divergent molecular networks in spores and seeds. New Phytol 211:952–966PubMedPubMedCentralCrossRefGoogle Scholar
  106. von Stackelberg M, Rensing SA, Reski R (2006) Identification of genic moss SSR markers and a comparative analysis of twenty-four algal and plant gene indices reveal species-specific rather than group-specific characteristics of microsatellites. BMC Plant Biol 6:9CrossRefGoogle Scholar
  107. Weismann D, Hartvigsen K, Lauer N, Bennet KL, Scholl HPN, Issa PC, Cano M, Brandstatter H, Tsimikas S, Skerka C, Superti-Furga G, Handa JT, Zipfel PF, Witztum JL, Binder CJ (2011) Complement factor H binds malondialdehyde epitopes and protects from oxidative stress. Nature 478:76–81PubMedPubMedCentralCrossRefGoogle Scholar
  108. Wiedemann G, van Gessel N, Köchl F, Hunn L, Schulze K, Maloukh L, Nogué F, Decker EL, Hartung F, Reski R (2018) RecQ helicases function in development, DNA-repair and gene targeting in Physcomitrella patens. Plant Cell 30:717–736PubMedPubMedCentralCrossRefGoogle Scholar
  109. Zhan X, Zhang Y-H, Chen D-F, Simonsen HT (2014) Metabolic engineering of the moss Physcomitrella patens to produce the sesquiterpenoids patchoulol and α/β-santalene. Front Plant Sci 5:636PubMedPubMedCentralCrossRefGoogle Scholar
  110. Zheng Z, Gao S, Huan L, Wang GC (2018) Diluted seawater affects phytohormone receptors and maintains the protonema stage in Physcomitrella patens. Plant J 93:119–130PubMedCrossRefGoogle Scholar
  111. Zimmer AD, Lang D, Buchta K, Rombauts S, Nishiyama T, Hasebe M, Peer YV de, Rensing SA, Reski R (2013) Reannotation and extended community resources for the genome of the non-seed plant Physcomitrella patens provide insights into the evolution of plant gene structures and functions. BMC Genom 14:498CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Plant Biotechnology, Faculty of BiologyUniversity of FreiburgFreiburgGermany
  2. 2.BIOSS, Centre for Biological Signalling StudiesFreiburgGermany
  3. 3.Mosspiration Biotech IVSHørsholmDenmark
  4. 4.Department of Biotechnology and BiomedicineTechnical University of DenmarkLyngbyDenmark

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