1 Introduction
Yeast is a valuable microbial cell factory in biosynthesis of industrial products, such as biofuels, organic acids terpenoids, abscisic acid and flavonoids[1-5]. However, cell growth rate and product yield are limited in industrial fermentation processes, due to the issues such as heat shock, product toxicities and oxidative stress[6]. Some key reasons are these stresses can cause reactive oxygen species (ROS) accumulation, protein denaturation, chromosome damage, cell membrane destruction and dysmetabolism[1, 7, 8]. Despite the intensive use of physical and chemical ways to reduce the undermines, there are still significant challenges from fermentation process, including the relatively high production cost of extra operations and environment pollution. TFs are important components of complex signaling networks and they can interact with kinases, other transcription factors and metabolite molecules to transmit signals to the nucleus under stress stimulation. So, TFs have the potential to control gene transcription in a specific temporal and spatial scales to improve the complex phenotype [9, 10]. Recent studies indicate that transcription factor (TFs) have focused on regulating transcriptional level of tolerance genes that contribute to contribute to stress tolerance traits. Therefore, improving the strains tolerance by stress-responded TFs engineering will markedly deal with stress on metabolic networks [11].
Simultaneously, an enhanced understanding of TFs engineering in combination with synthetic biology theory will improve the applications of native TFs and enable the further development of synthetic biology tools. Native stress responsive TFs operated by genetic engineering, helps promote the metabolism of the chassis toward the direction of improving strains tolerance and industrial production. With the new strategies of using TFs springing up, artificial transcription factors (ATFs) which fuse a series of native TFs functional domains have extensive functions. They can make up for the shortcomings of natural TFs and broaden the application fields of TFs engineering. In this review, we briefly review the TF-related molecular traits of cellular stress responses and TFs engineering based on TFs regular pattern in improving the stress tolerance and efficiency in biomanufacturing. We also summarize the most recent applications of Artificial transcription factors (ATFs) originated from native TFs, which can either be better used as parts to fine tuning gene expression or for switch to control genes in metabolic pathways than before. Even, it has been invented as devices to quantitatively evaluate metabolites content. Lastly, we discuss the understanding in achieving strains biomanufacturing and innovations of synthetic biology tools by TFs.