Team:ZJU-China/Application & Significance



    As heterologous protein expression is becoming more and more commonplace and constitutes an indispensible part of modern biotechnology, the request for a more reliable, predictable and successful expression is impending. It's fairly likely that a protein obtained from one species might fail to be expressed at all in another organism. The need for higher expression is particularly great when related with industry in which the improved expression of the desired protein will greatly enlarge company's profits and improve people's living standards. In such a practical aspect, our software Bach is helpful and convenient for both daily laboratory works and production industries. The optimization of coding sequences by Bach can provide users with not only a new sequence of optimal translation rates but also a quantitative analysis of the improved performance in terms of RiPS.

    In synthetic biology, our work makes a big step towards the next generation of standardization and quantification. The biobricks that each iGEM team uses and submits each year are from various organisms, thus of diverse genetic backgrounds and codon biases. As codon bias plays an important role in translation rate, such diversity may subject different biobricks (coding sequence) to diverse and unpredictable RiPS when put into a particular host organism to construct a complex genetic circuit. Therefore, the need emerges to unify the codon bias to suit the host organism of desire. Meanwhile, Bach serves as a desirable and convenient tool to eliminate such generic backgrounds and noise, which is essential for both the present and future developments of synthetic biology. In designing simple systems at present, Bach can prevent cases when the codon bias of a certain biobrick is so distant from the host that its expression is greatly affected and leads to the unexpected chaos and failure of the system.

    Compared with other current sequence optimizer software, our software Bach has also made a few breakthroughs. Though current sequence optimizer software can optimize coding sequences as well, they all fail to demonstrate how much translation rate has actually changed computationally or theoretically. Based on a quantitative mathematical model, Bach can make quantitative estimations of translation rates in terms of RiPS to more vividly illustrate the difference each optimization has made in the aspect of translation. Another forte of Bach is its diverse choice of methods for optimization, so that it can cater to different needs of users. As there's no set standard for optimization of coding sequences at present, multiple approaches combined in one single software can certainly offer users more freedom and make the optimization process itself more sensible and applicable.

    At last, we believe that with the development of synthetic biology and new technologies, genetic circuits will be increasingly complex and the demand for its quantitative predictability will be larger and larger. At the same time, the cost of DNA synthesis will surely become cheaper and cheaper. That's when Bach will be able to realize its full potential to make a difference.