Synthetic Biology: Reports from CSHA 2016 and More

Abstract

The past two decades have witnessed immense progress in synthetic biology, including development of tools for genetic manipulation, elucidation of design principles for designing robust gene circuits, tools to analyze dynamics of engineered cells, and application of engineered cells in diverse contexts. A Cold Spring Harbor Asia Conference on Synthetic Biology was held in Suzhou China, in November 2016, to showcase a subset of such developments.To highlight these progresses, the Biotechnology Journal invited a number of review research articles to form the basis of a special issue on Synthetic Biology.These articles illustrate the progress in multiple aspects. For example, it is well appreciated that a major application arm for synthetic biology is in the engineering of metabolic pathways for producing valuable products. In this framework, Okano and colleagues [1] engineer the Lactobacillus plantarum NCIMB 8826 to enhance production of optically pure L-lactic acid from raw starch by deletion of lactate dehydrogenase, and the operon encoding lactate racemase (larA-E), and furthermore introduced the alpha-amylase from Streptococcus bovis 148 to increase the production level and to obtain 98.6% of optically pure lactic acid. Liu and colleagues [2] use rational metabolic engineering to increase L-cysteine production by 14-fold in Escherichia coli by modifying transport, sulfur supply, enhance precursor pathway, and reduce L-cysteine degradation.Interestingly, Thomson and coworkers [3] dissect the quiescent (Q-Cell) E. coli, known to have enhanced production of 3-hydroxybutyrate, for its proteomics and metabolomics. This analysis has made it possible for the potential use of Q-cells as a production host for a wide range of chemical compounds. Similarly, Hirasawa and colleagues [4] have analyzed the transcriptome and metabolome of Corynebacterium glutamicum to understand the mechanism of penicillin-induced glutamic acid production. Another way to examine the metabolism of a production host is by perturbation of a metabolic steady-state and the detailed analysis of the subsequent metabolic response. Tröndle and coworkers [5] perturb the supply of substrate (e.g., phosphoenolpyruvate) in E. coli to understand its impact on Lphenylalanine production and identified substrate transporters as important aspects to consider. Importantly, this method can be applied to other compound processes.The engineering of diverse gene circuits depends on the development of well characterized parts and devices and the corresponding chassis cells. To this end, McCutcheon and colleagues [6] demonstrate the development of a set of CRISPRCas-based devices for tunable control of gene expression. Aparicio and colleagues [7] use a CRISPR-Cas9 system to enable effective genetic engineering of Pseudomonas putida, which is emerging as an increasingly popular cell-factory platform for metabolic engineering and recombinant protein synthesis.Microfluidics has become an indispensable tool in quantitative analysis of single cells or cell populations. It...