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Applied Microbiology and Biotechnology

, Volume 100, Issue 14, pp 6193–6208 | Cite as

Kluyveromyces marxianus as a host for heterologous protein synthesis

  • Andreas K. Gombert
  • José Valdo MadeiraJr.
  • María-Esperanza Cerdán
  • María-Isabel González-SisoEmail author
Mini-Review

Abstract

The preferentially respiring and thermotolerant yeast Kluyveromyces marxianus is an emerging host for heterologous protein synthesis, surpassing the traditional preferentially fermenting yeast Saccharomyces cerevisiae in some important aspects: K . marxianus can grow at temperatures 10 °C higher than S. cerevisiae, which may result in decreased costs for cooling bioreactors and reduced contamination risk; has ability to metabolize a wider variety of sugars, such as lactose and xylose; is the fastest growing eukaryote described so far; and does not require special cultivation techniques (such as fed-batch) to avoid fermentative metabolism. All these advantages exist together with a high secretory capacity, performance of eukaryotic post-translational modifications, and with a generally regarded as safe (GRAS) status. In the last years, replication origins from several Kluyveromyces spp. have been used for the construction of episomal vectors, and also integrative strategies have been developed based on the tendency for non-homologous recombination displayed by K. marxianus. The recessive URA3 auxotrophic marker and the dominant KanR are mostly used for selection of transformed cells, but other markers have been made available. Homologous and heterologous promoters and secretion signals have been characterized, with the K. marxianus INU1 expression and secretion system being of remarkable functionality. The efficient synthesis of roughly 50 heterologous proteins has been demonstrated, including one thermophilic enzyme. In this mini-review, we summarize the physiological characteristics of K. marxianus relevant for its use in the efficient synthesis of heterologous proteins, the efforts performed hitherto in the development of a molecular toolbox for this purpose, and some successful examples.

Keywords

Kluyveromyces marxianus Thermotolerant yeast Cell factory Heterologous protein synthesis Heterologous protein secretion Eukaryotic post-translational modifications 

Notes

Acknowledgments

General support to the group EXPRELA was funded by Xunta de Galicia (Consolidación D.O.G. 10-10-2012. Contract Number: 2012/118) co-financed by FEDER. We also acknowledge support from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), São Paulo, Brazil, through grant number 2015/14109-0. JVM-Jr. acknowledges a PNPD scholarship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brasília, Brazil.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

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

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Andreas K. Gombert
    • 1
  • José Valdo MadeiraJr.
    • 1
  • María-Esperanza Cerdán
    • 2
  • María-Isabel González-Siso
    • 2
    Email author
  1. 1.School of Food EngineeringUniversity of CampinasCampinasBrazil
  2. 2.Grupo EXPRELA, Centro de Investigacións Científicas Avanzadas (CICA), Departamento de Bioloxía Celular e Molecular, Facultade de CienciasUniversidade da CoruñaA CoruñaSpain

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