Strategies for genetic engineering of yeast to secrete more protein

What is it about?

Yeast is the preferred cell factory for the production of a wide range of fine chemicals, metabolites, proteins and bulk biofuels. Yeast uses simple sugars to grow and produce these products of interest. These simple sugars are expensive and may lead to competition with food production. To improve the industrial scale economics of this process, inexpensive feedstocks like cellulose-rich plant biomass waste is an attractive alternative. Wild yeasts are unable to utilise the complex cellulose molecules in biomass, but can be genetically engineered to do so. Many engineered yeast strains that have been made over the years are able to utilise cellulose, however the efficiency of the process remains below the industrial requirements for the feasible production of biofuels. The predominant reasons for this low efficiency relates to the limited amount of engineered enzymes to allow the breakdown of the cellulose. To this end, many studies have started to focus on ways to increase the production of these enzymes by engineered yeast. In this review, we give an overview of the recent engineering attempts to increase the production of the enzymes required by yeast to rapidly and efficiently break down cellulose to produce other useful compounds.

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Why is it important?

This review gives a brief overview of the secretion pathway of yeast and highlights the most important engineering targets for enhancing protein secretion. The benefits and shortcomings of recent engineering approaches to improve secretion are discussed in detail. The review also contains an extensive list (Table 1 and Supplementary documents) of all published rational secretion pathway engineering approaches up to date, including information on the respective gene targets, the alterations to these genes and the level of secretion improvement that was achieved.