bioRxiv Science⌕ Search

Biology subjects

Teparic, R.

Publications and source records attributed to Teparic, R..

2 recordsLinked to original sources

Salt-enhanced surface display in the halotolerant yeast Debaryomyces hansenii

The halo-, xero-, and osmotolerant oleaginous yeast Debaryomyces hansenii can grow in extreme environments, with some isolates tolerating up to 4 M NaCl. As such, it could serve as a robust microbial chassis for non-sterile biotechnological processes based on seawater or saline side streams. However, its biotechnological toolbox lacks key genetic tools, particularly for inducible expression, secretion, and covalent anchoring of proteins to the outer cell surface. To address this gap, we characterised how growth in a medium supplemented with 1 M NaCl remodels the D. hansenii cell wall. We also developed strong constitutive, stationary-phase, and NaCl-inducible expression vectors, and designed protein tags for C- and N-terminal cell wall anchoring. These tools enabled functional surface display of {beta}-lactamase, acetylxylan esterase, and lipase A via native GPI-dependent and heterologous Pir-based anchors, while immunoblotting detected the reporters in both covalently and non-covalently bound cell wall fractions. Activities of surface-displayed enzymes increased by more than 80 % under hypersaline conditions, while DhCcw12-based C-terminal anchoring outperformed Pir-based N-terminal anchoring. Thus, we retooled the D. hansenii cell wall into a catalytically active biointerface and established this yeast as an osmotolerant chassis for hypersaline surface display.

molecular biology↗

Boosting N-terminally anchored yeast surface display via structural insights into S. cerevisiae Pir proteins

Surface display co-opts yeasts innate ability to embellish its cell wall with mannoproteins, thus converting the yeasts outer surface into a growing and self-sustaining catalyst. However, the efficient toolbox for converting the enzyme of interest into its surface-displayed isoform is currently lacking, especially if the isoform needs to be anchored to the cell wall near the isoforms N-terminus. Aiming to advance such N-terminally anchored surface display, we employed in silico and machine-learning strategies to study the 3D structure, function, genomic organisation, and evolution of the Pir protein family, whose members evolved to covalently attach themselves near their N-terminus to the {beta}-1,3-glucan of the cell wall. Through the newly-gained insights, we rationally engineered 14 S. cerevisiae Hsp150 (Pir2)-based fusion proteins. We quantified their performance, uncovering guidelines for efficient yeast surface display while developing a construct that promoted a 2.5-fold more efficient display than the full-length Hsp150 and a Pir-tag, i.e., a peptide spanning only 4.5 kDa but promoting as efficient surface display as the full-length Hsp150. These constructs fortify the existing surface display toolbox, allowing for a prompt and routine refitting of any protein into its N-terminally anchored isoform. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=137 SRC="FIGDIR/small/538238v1_ufig1.gif" ALT="Figure 1"> View larger version (60K): org.highwire.dtl.DTLVardef@909e7aorg.highwire.dtl.DTLVardef@9480ceorg.highwire.dtl.DTLVardef@1945bdcorg.highwire.dtl.DTLVardef@11ae505_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗