Systems biology for industrial applications

Cover illustration: Systems biology for industrial applications. Biofuel production from lignocellulosic biomass is one of the key topics in industrial systems biology. This issue of BTJ edited by Jens Nielsen (Chalmers, Gothenburg, Sweden) covers reviews and original articles on systems biology approaches for biofuel production, i.e., metabolic flux analysis in Clostridia species as well as advancing metabolic engineering of yeasts, and sustainable chemistry in Corynebacterium glutamicum and microalgae. Image provided by Payam Ghiaci, Chalmers, Sweden.     

Systems biology: new institute and applications

The Yale Systems Biology Institute (YSBI) sponsored its first symposium at the university's West Campus in October 2010. The symposium served to provide Yale's scientific community with a glimpse into the wide range of research at the forefront of this interdisciplinary field. YSBI was conceived less than a year ago, and the event was the perfect forum for its debut, both at Yale and in the U.S. scientific community. This article includes a brief overview of the different topics presented at the symposium, followed by a discussion of the advantages and challenges of practical application of systems biology.     

Developing cell-free biology for industrial applications

Although cell-free protein synthesis has been practiced for decades as a research tool, only recently have advances suggested its feasibility for commercial protein production. This focused review, based on the 2005 Amgen Award lecture, summarizes the relevant progress from the Swartz laboratory. When our program began, projected costs were much too high, proteins with disulfide bonds could not be folded effectively, and no economical scale-up technologies were available. By focusing on basic biochemical reactions and by controlling cell-free metabolism, these limitations have been methodically addressed. Amino acid supply has been stabilized and central metabolism activated to dramatically reduce substrate costs. Control of the sulfhydral redox potential has been gained and a robust disulfide isomerase added to facilitate oxidative protein folding. Finally, simple scale-up technologies have been developed. These advances not only suggest production feasibility for pharmaceutical proteins, they also provide enabling technology for producing patient-specific vaccines, for evolving new enzymes to enable biological hydrogen production from sunlight, and for developing new and highly effective water filters. Although many challenges remain, this newly expanded ability to activate and control protein production holds much promise for both research and commercial applications.     

Systems biology for industrial strains and fermentation processes--example: amino acids

Systems biology is attracting significant interest finding applications not only in pharmaceutical development but also for basic studies on microbial systems. The latter often concentrate on the quantitative understanding of global regulation phenomena. So far, these activities are dominated by academic groups basically mirroring the necessity to prepare the sound scientific understanding first, before industrial applications can be derived later. However, this short-term view may not be sufficient because systems biology already offers numerous benefits for industrial applications, provided that special constraints are considered. This contribution indicates some of the constraints worth noticing when industrial systems biology projects are carried out. Consequently, differences in project structure and goals between purely academic and industrial systems biology projects are outlined.     

Phage integrases: biology and applications

Phage integrases are enzymes that mediate unidirectional site-specific recombination between two DNA recognition sequences, the phage attachment site, attP, and the bacterial attachment site, attB. Integrases may be grouped into two major families, the tyrosine recombinases and the serine recombinases, based on their mode of catalysis. Tyrosine family integrases, such as lambda integrase, utilize a catalytic tyrosine to mediate strand cleavage, tend to recognize longer attP sequences, and require other proteins encoded by the phage or the host bacteria. Phage integrases from the serine family are larger, use a catalytic serine for strand cleavage, recognize shorter attP sequences, and do not require host cofactors. Phage integrases mediate efficient site-specific recombination between two different sequences that are relatively short, yet long enough to be specific on a genomic scale. These properties give phage integrases growing importance for the genetic manipulation of living eukaryotic cells, especially those with large genomes such as mammals and most plants, for which there are few tools for precise manipulation of the genome. Integrases of the serine family have been shown to work efficiently in mammalian cells, mediating efficient integration at introduced att sites or native sequences that have partial identity to att sites. This reaction has applications in areas such as gene therapy, construction of transgenic organisms, and manipulation of cell lines. Directed evolution can be used to increase further the affinity of an integrase for a particular native sequence, opening up additional applications for genomic modification.     

Metagenomics and industrial applications

Different industries have different motivations to probe the enormous resource that is uncultivated microbial diversity. Currently, there is a global political drive to promote white (industrial) biotechnology as a central feature of the sustainable economic future of modern industrialized societies. This requires the development of novel enzymes, processes, products and applications. Metagenomics promises to provide new molecules with diverse functions, but ultimately, expression systems are required for any new enzymes and bioactive molecules to become an economic success. This review highlights industrial efforts and achievements in metagenomics.     

系统生物学--后基因组时代的生物学

随着人类基因组计划的完成,生物学已由微观的分子研究转向生物整体性研究,系统生物学应运而生。讨论了系统生物学的产生、特点、研究内容和方法。     

BioMEMS and cellular biology: perspectives and applications

The ability to culture cells has revolutionized hypothesis testing in basic cell and molecular biology research. It has become a standard methodology in drug screening, toxicology, and clinical assays, and is increasingly used in regenerative medicine. However, the traditional cell culture methodology essentially consisting of the immersion of a large population of cells in a homogeneous fluid medium and on a homogeneous flat substrate has become increasingly limiting both from a fundamental and practical perspective. Microfabrication technologies have enabled researchers to design, with micrometer control, the biochemical composition and topology of the substrate, and the medium composition, as well as the neighboring cell type in the surrounding cellular microenvironment. Additionally, microtechnology is conceptually well-suited for the development of fast, low-cost in vitro systems that allow for high-throughput culturing and analysis of cells under large numbers of conditions. In this interview, Albert Folch explains these limitations, how they can be overcome with soft lithography and microfluidics, and describes some relevant examples of research in his lab and future directions.     

Systems biology and cancer: promises and perils

Systems biology uses systems of mathematical rules and formulas to study complex biological phenomena. In cancer research there are three distinct threads in systems biology research: modeling biology or biophysics with the goal of establishing plausibility or obtaining insights, modeling based on statistics, bioinformatics, and reverse engineering with the goal of better characterizing the system, and modeling with the goal of clinical predictions. Using illustrative examples we discuss these threads in the context of cancer research.