Comparison of secretory signal peptides for heterologous protein expression in microalgae: Expanding the secretion portfolio for Chlamydomonas reinhardtii

PLoS One. 2018 Feb 6;13(2):e0192433. doi: 10.1371/journal.pone.0192433. eCollection 2018.

Abstract

Efficient protein secretion is a desirable trait for any recombinant protein expression system, together with simple, low-cost, and defined media, such as the typical media used for photosynthetic cultures of microalgae. However, low titers of secreted heterologous proteins are usually obtained, even with the most extensively studied microalga Chlamydomonas reinhardtii, preventing their industrial application. In this study, we aimed to expand and evaluate secretory signal peptides (SP) for heterologous protein secretion in C. reinhardtii by comparing previously described SP with untested sequences. We compared the SPs from arylsulfatase 1 and carbonic anhydrase 1, with those of untried SPs from binding protein 1, an ice-binding protein, and six sequences identified in silico. We identified over 2000 unique SPs using the SignalP 4.0 software. mCherry fluorescence was used to compare the protein secretion of up to 96 colonies for each construct, non-secretion construct, and parental wild-type cc1690 cells. Supernatant fluorescence varied according to the SP used, with a 10-fold difference observed between the highest and lowest secretors. Moreover, two SPs identified in silico secreted the highest amount of mCherry. Our results demonstrate that the SP should be carefully selected and that efficient sequences can be coded in the C. reinhardtii genome. The SPs described here expand the portfolio available for research on heterologous protein secretion and for biomanufacturing applications.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chlamydomonas reinhardtii / metabolism*
  • Chlamydomonas reinhardtii / physiology
  • Photosynthesis
  • Plant Proteins / metabolism*

Substances

  • Plant Proteins

Grants and funding

This work was supported by funding from the US Department of Energy Algae PEAK award EE0008246 (https://energy.gov/) (SM) and the São Paulo Research Foundation (FAPESP) grant 2013/18224-2 (http://www.fapesp.br/en/) (JVDM). JVDM was funded by the PhD grant from FAPESP. The funding source was not involved in study design, data collection, analysis and interpretation of data, in the writing of the report, nor in the decision to submit the article for publication.