In this issue: Biotechnology Journal 7/2010

Abstract

AbstractPichia pastoris metabolic modelSohn et al., Biotechnol. J. 2010, 5, 705–715The methylotrophic yeast Pichia pastoris become a platform for producing heterologous recombinant proteins of pharmaceutical importance, thanks to its ability to reproduce post‐translational modification similar to higher eukaryotes. With the recent release of the full genome sequence for P. pastoris, in‐depth study of its functions has become feasible. The groups of Sang Yup Lee (Daejeon, Korea) and Diethard Mattanovich (Vienna, Austria) present the first reconstruction of a genome‐scale metabolic model of the eukaryote P. pastoris type strain DSMZ 70382, PpaMBEL1254. It consists of 1254 metabolic reactions and 1147 metabolites compartmentalized into eight different regions which represent organelles. They incorporated equations describing the production of two heterologous proteins, human serum albumin and human superoxide dismutase, and analyzed for the impact of oxygen limitation on protein production.A blueprint of lifeHenry et al., Biotechnol. J. 2010, 5, 695–704The de novo synthesis and implantation of an entire prokaryotic genome to create a living synthetic cell represents a breakthrough in the field of systems and synthetic biology. The challenge is to construct a blueprint for the first truly synthetic organism containing only a minimal genome. Chris Henry, Ross Overbeek and Rick L. Stevens review the significant progress made in the design and creation of a minimal organism. They discuss how comparative genomes, gene essentiality data, naturally small genomes and metabolic modeling are being applied to produce a catalogue of the biological functions essential for life. Minimal gene sets from three published sources with functions identified in 13 existing gene essentiality datasets are compared. They also examine how genome‐scale metabolic models can been applied to design a minimal metabolism for growth in simple and complex media.Exoenzymes cooperate or cheatSchuster et al., Biotechnol. J. 2010, 5, 751–758Extracellular enzymes (exoenzymes) are needed for many biotechnologically relevant processes, like secreted cellulases for biofuel production. Productivity is often reduced by “cheater” mutants, which are deficient in exoenzyme production and benefit from the product provided by the “cooperating” cells. Anja Schroeter and colleagues from Jena (Germany) and Tel Aviv (Israel) present a game‐theoretical model to analyze the population structure and exoenzyme productivity for biotechnological applications. They predict three scenarios: i) when the metabolic effort for exoenzyme production is low all cells cooperate; ii) at intermediate metabolic costs cooperators and cheaters coexist; and iii) at high costs all cells use the cheating strategy. These three regimes correspond to the harmony game, snowdrift game, and prisoner's dilemma, respectively. While also taking into account cell density, the model predicts that engineered microbial strains play the “harmony game” when the conditions are appropriate.