Editorial: Biochemical and molecular engineering.

Abstract

George Guo-Qiang Chen and Brian Pfleger This special issue of Biotechnology Journal is a compilation of some of the latest and hottest research, presented at the “Biochemical and Molecular Engineering Conference” (ECI BME XVIII) held in summer 2013 in Beijing, China. The special issue covers a wide range of topics, including synthetic biology, metabolic engineering and their application in the production of chemicals. In addition, advances in siRNA and medical fields are reported. A popular application of synthetic biology is the design and assembly of genetic circuits capable of implementing the logic functions more commonly associated with electrical circuits or computing. Over the past ten years, the interest of electrical engineers in synthetic biology has led to the demonstration of nearly every logic function in a biological host. In this issue, Roquet and Lu [1] summarize the state of biologically encoded circuits and provide their view of the strategies for implementing digital and analog circuits. The production of fuels and chemicals in microorganisms integrates the fields of metabolic engineering, systems biology, synthetic biology, and bioprocess engineering. In this issue, Borodina and Nielsen [2] review the current status of chemical production in the model yeast, Saccharomyces cerevisiae, highlighting the influence of each of these research fields and presenting case studies for producing three natural compounds, lactic acid, succinic acid and cis-cis-muconic acid. The combination of these fields has also greatly broadened the scope of what molecules can be produced in a living organism. The article by Lee and co-workers [3] demonstrates the use of trans-acting regulators to rapidly engineer strains of Escherichia coli to produce phenol, a chemical that is commonly used in extraction of biological molecules from cells. Cell-free protein synthesis (CFPS) has become a promising alternative to engineering live cells. By combining cell extracts with essential genetic and biochemical components, the protein synthesis process can be performed in the absence of cell growth, thereby by-passing issues associated with toxicity, impaired growth rate, transport, and other cell specific complications. In two separate articles, Jewett and co-workers [4] present and optimize a cell-free system based on yeast extracts that enhance the production of eukaryotic proteins. At the same time, high-throughput CFPS is helping to address the increasing discrepancy between genome sequence data and their translation products. Jewett and co-worker [5] report a com-bined cell-free transcription-translation (Tx/Tl) system from Saccharomyces cerevisiae that is suitable for such efforts. They demonstrate the ability to enable translation initiation in a cap-independent manner. The CFPS method has the potential to rapidly prepare tens to thousands of DNA templates without time-consuming cloning work and holds promise for fast and convenient optimization of expression constructs, study of internal ribosome entry site (IRES), and production of protein libraries for genome scale studies. We would like to thank the authors who have contributed to this issue and express our excitement for the upcoming ECI BME XIX meeting in 2015. Zhu and colleagues [6] use small interfering RNA (siRNA) targeting to the RPL39 gene to determine the effects of the RPL39 gene on growth of pancreatic cancer PANC-1 and BxPC-3 cells in vitro and in vivo. They show that knockdown of RPL39 expression with RPL39-siRNA suppressed cell proliferation and specifically enhanced cell apoptosis significantly in both PANC-1 and BxPC-3 cells. This suggests that siRNA against the RPL39 gene may be of value for gene therapy of pancreatic cancer. The blood–brain barrier (BBB) represents an obstacle in targeting and delivering therapeutics to the central nervous system. In order to discover new BBB-targeting molecules, Shusta and colleagues [7] pan a phage displayed nonimmune human single-chain antibody fragment (scFv) library against a representative BBB model comprising hydrocortisone-treated primary rat brain endothelial cells and identify two new antibodies capable of binding antigens that are expressed at the BBB in vivo. Cardiomyocytes (CM) derived from human embryonic stem cells (hESC) are used for cardio-toxicity evaluation and tested in many preclinical trials for their potential use in regenerative therapeutics. An automated time-resolved video analysis and management system (TVAMS) is reported by Ting and coworkers [8] for the evaluation of human embryonic stem cells hESC differentiation to CM. For over 50 years, the lack of α-ketoglutarate dehydrogenase has led to the belief that cyanobacteria have an incomplete TCA cycle. Recent in vitro enzymatic experiments suggest that this cycle may in fact be closed. Tang and colleagues [9] employ 13C isotopomers to delineate pathways in the cyanobacterium Synechocystis sp. PCC 6803. They observe a direct in vivo transformation of α-ketoglutarate to succinate. The results improve the understanding of the versatile metabolism in cyanobacteria and shed light on their application for photo-biorefineries. In summary, the field of biotechnology continues to grow with focus on many of society's grand challenges – energy, sustainability, health, medicine, environment – aspects that lead to a higher quality of life. Contributions are coming from all over the world and meetings such as the ECI BME conference will continue to be a critical hub of interaction, collaboration, and dissemination of research knowledge for the field. We would like to thank the authors who have contributed to this issue and express our excitement for the upcoming ECI BME XIX meeting in 2015, which will be held in Los Cabos, Mexico. Prof. George Guo-Qiang Chen Tsinghua University, Beijing, China E-mail: chengq@mail.tsinghua.edu.cn Prof. Brian Pfleger University of Wisconsin-Madison, WI, USA E-mail: pfleger@engr.wisc.edu