Transketolase 1 (TKL1) is a pivotal protein involved in diverse biological processes, representing an isoform of transketolase crucial for the pentose phosphate pathway (PPP) [1]. The PPP holds significance in generating NADPH and ribose-5-phosphate, critical for nucleotide and lipid synthesis, alongside maintaining cellular redox equilibrium [2]. Notably, TKL1's association with tumor-cell proliferation is evident, with its overexpression noted in cancer, particularly linked to poor prognosis in colorectal and gastric cancer [3][4]. Moreover, its involvement in glucose fermentation within the PPP suggests a role in cancer metabolism [5]. Under oxidative and osmotic stress, TKL1 exhibits altered expression and activities, indicating its participation in stress response mechanisms [6][7]. In yeast, TKL1 emerges as the principal transketolase of the PPP, emphasizing its importance in cellular metabolism [8]. Furthermore, TKL1, among other non-oxidative PPP enzymes, has been targeted for overexpression to augment ethanol production from mixed glucose/xylose mediums in recombinant Saccharomyces cerevisiae [9]. These observations delineate TKL1's multifaceted roles spanning cancer biology, stress response, and metabolic engineering.
References:
[1] C. Lu and T. Jeffries, "Shuffling of promoters for multiple genes to optimize xylose fermentation in an engineered saccharomyces cerevisiae strain", Applied and Environmental Microbiology, vol. 73, no. 19, p. 6072-6077, 2007. https://doi.org/10.1128/aem.00955-07
[2] B. Johansson and B. Hahn-Hägerdal, "The non-oxidative pentose phosphate pathway controls the fermentation rate of xylulose but not of xylose in tmb3001", Fems Yeast Research, vol. 2, no. 3, p. 277-282, 2002. https://doi.org/10.1016/s1567-1356(02)00114-9
[3] K. Ahopelto, C. Böckelman, J. Hagström, S. Koskensalo, & C. Haglund, "Transketolase-like protein 1 expression predicts poor prognosis in colorectal cancer", Cancer Biology & Therapy, vol. 17, no. 2, p. 163-168, 2015. https://doi.org/10.1080/15384047.2015.1121347
[4] K. Ahopelto, A. Laitinen, J. Hagström, C. Böckelman, & C. Haglund, "Transketolase-like protein 1 and glucose transporter 1 in gastric cancer", Oncology, vol. 98, no. 9, p. 643-652, 2020. https://doi.org/10.1159/000507350
[5] R. Wittig and J. Coy, "The role of glucose metabolism and glucose-associated signalling in cancer", Perspectives in Medicinal Chemistry, vol. 1, p. 1177391X0700100, 2007. https://doi.org/10.1177/1177391x0700100006
[6] E. Kowalska, M. Kujda, N. Wolak, & A. Kozik, "Altered expression and activities of enzymes involved in thiamine diphosphate biosynthesis in saccharomyces cerevisiae under oxidative and osmotic stress", Fems Yeast Research, vol. 12, no. 5, p. 534-546, 2012. https://doi.org/10.1111/j.1567-1364.2012.00804.x
[7] H. Iwata, Y. Kobayashi, D. Mizushima, T. Watanabe, J. Ogihara, & T. Kasumi, "Complementary function of two transketolase isoforms from moniliella megachiliensis in relation to stress response", Amb Express, vol. 7, no. 1, 2017. https://doi.org/10.1186/s13568-017-0342-0
[8] K. Slekar, D. Kosman, & V. Culotta, "The yeast copper/zinc superoxide dismutase and the pentose phosphate pathway play overlapping roles in oxidative stress protection", Journal of Biological Chemistry, vol. 271, no. 46, p. 28831-28836, 1996. https://doi.org/10.1074/jbc.271.46.28831
[9] Y. Kobayashi, T. Sahara, S. Ohgiya, Y. Kamagata, & K. Fujimori, "Systematic optimization of gene expression of pentose phosphate pathway enhances ethanol production from a glucose/xylose mixed medium in a recombinant saccharomyces cerevisiae", Amb Express, vol. 8, no. 1, 2018. https://doi.org/10.1186/s13568-018-0670-8
