Fig. 1

Overview of key steps explored in this study to improve peptide secretion in Sb. (1) Transcription of the gene encoding for the secreted protein, located on the genome or on multicopy plasmids. (2) Translocation and modifications that occur in the ER. Nascent peptides are translocated to the ER post-translationally or co-translationally. This route is dictated by the secretion signal located at the N-terminus of the secreted protein. Within the ER lumen, proteins are modified through folding and gluco/mannosylation. Mis- and unfolded proteins are subject to ERAD, in which they are retro-translocated from the ER to the cytoplasm and degraded by the proteasome. (3) Protein trafficking from the ER to the Golgi and modification within the Golgi. Properly folded/modified proteins are transported to the Golgi via COPII vesicles. Retrograde transport within the Golgi and from the Golgi to the ER is regulated by COPI vesicles. Proteins are further gluco/mannosylated in the Golgi. (4) Protein trafficking between the Golgi and vacuole and exocytosis. Secretory proteins are trafficked from the Golgi to the exterior through vesicles recognized by receptors found on the cell membrane. Secreted proteins are often degraded by proteases secreted into the culture medium. The large retromeric complex regulates protein missorting from the Golgi to the endosome, which later develops into the vacuole. Proteins sorted to the vacuole are subject to degradation by vacuolar proteases