Second generation Pichia pastoris strain and bioprocess designs.

Yeast was the first microorganism used by mankind for biotransformation processes that laid the foundations of industrial biotechnology. In the last decade, Pichia pastoris has become the leading eukaryotic host organism for bioproduct generation. Most of the P. pastoris bioprocess operations has been relying on toxic methanol and glucose feed. In the actual bioeconomy era, for sustainable value-added bioproduct generation, non-conventional yeast P. pastoris bioprocess operations should be extended to low-cost and renewable substrates for large volume bio-based commodity productions. In this review, we evaluated the potential of P. pastoris for the establishment of circular bioeconomy due to its potential to generate industrially relevant bioproducts from renewable sources and waste streams in a cost-effective and environmentally friendly manner. Furthermore, we discussed challenges with the second generation P. pastoris platforms and propose novel insights for future perspectives. In this regard, potential of low cost substrate candidates, i.e., lignocellulosic biomass components, cereal by-products, sugar industry by-products molasses and sugarcane bagasse, high fructose syrup by-products, biodiesel industry by-product crude glycerol, kitchen waste and other agri-food industry by products were evaluated for P. pastoris cell growth promoting effects and recombinant protein production. Further metabolic pathway engineering of P. pastoris to construct renewable and low cost substrate utilization pathways was discussed. Although, second generation P. pastoris bioprocess operations for valorisation of wastes and by-products still in its infancy, rapidly emerging synthetic biology tools and metabolic engineering of P. pastoris will pave the way for more sustainable environment and bioeconomy. From environmental point of view, second generation bioprocess development is also important for waste recycling otherwise disposal of carbon-rich effluents creates environmental concerns. P. pastoris high tolerance to toxic contaminants found in lignocellulosic biomass hydrolysate and industrial waste effluent crude glycerol provides the yeast with advantages to extend its applications toward second generation P. pastoris strain design and bioprocess engineering, in the years to come.

Differential Protein Interactome in Esophageal Squamous Cell Carcinoma Offers Novel Systems Biomarker Candidates with High Diagnostic and Prognostic Performance.

Esophageal squamous cell carcinoma (ESCC) is among the most dangerous cancers with high mortality and lack of robust diagnostics and personalized/precision therapeutics. To achieve a systems-level understanding of tumorigenesis, unraveling of variations in the protein interactome and determination of key proteins exhibiting significant alterations in their interaction patterns during tumorigenesis are crucial. To this end, we have described differential protein-protein interactions and differentially interacting proteins (DIPs) in ESCC by utilizing the human protein interactome and transcriptome. Furthermore, DIP-centered modules were analyzed according to their potential in elucidation of disease mechanisms and improvement of efficient diagnostic, prognostic, and treatment strategies. Seven modules were presented as potential diagnostic, and 16 modules were presented as potential prognostic biomarker candidates. Importantly, our findings also suggest that 30 out of the 53 repurposed drugs were noncancer drugs, which could be used in the treatment of ESCC. Interestingly, 25 of these, proposed as novel drug candidates here, have not been previously associated in a context of esophageal cancer. In this context, risperidone and clozapine were validated for their growth inhibitory potential in three ESCC lines. Our findings offer a high potential for the development of innovative diagnostic, prognostic, and therapeutic strategies for further experimental studies in line with predictive diagnostics, targeted prevention, and personalization of medical services in ESCC specifically, and personalized cancer care broadly.

Enzymes for Efficient CO2 Conversion.

The accumulation of carbon dioxide in the atmosphere as a result of human activities has caused a number of adverse circumstances in the world. For this reason, the proposed solutions lie within the aim of reducing carbon dioxide emissions have been quite valuable. However, as the human activity continues to increase on this planet, the possibility of reducing carbon dioxide emissions decreases with the use of conventional methods. The emergence of compounds than can be used in different fields by converting the released carbon dioxide into different chemicals will construct a fundamental solution to the problem. Although electro-catalysis or photolithography methods have emerged for this purpose, they have not been able to achieve successful results. Alternatively, another proposed solution are enzyme based systems. Among the enzyme-based systems, pyruvate decarboxylase, carbonic anhydrase and dehydrogenases have been the most studied enzymes. Pyruvate dehydrogenase and carbonic anhydrase have either been an expensive method or were incapable of producing the desired result due to the reaction cascade they catalyze. However, the studies reporting the production of industrial chemicals from carbon dioxide using dehydrogenases and in particular, the formate dehydrogenase enzyme, have been remarkable. Moreover, reported studies have shown the existence of more active and stable enzymes, especially the dehydrogenase family that can be identified from the biome. In addition to this, their redesign through protein engineering can have an immense contribution to the increased use of enzyme-based methods in CO2 reduction, resulting in an enormous expansion of the industrial capacity.