Genome-scale resources for Thermoanaerobacterium saccharolyticum.

Background: Thermoanaerobacterium saccharolyticum is a hemicellulose-degrading thermophilic anaerobe that was previously engineered to produce ethanol at high yield. A major project was undertaken to develop this organism into an industrial biocatalyst, but the lack of genome information and resources were recognized early on as a key limitation.

Results: Here we present a set of genome-scale resources to enable the systems level investigation and development of this potentially important industrial organism.

Metabolic engineering of a tyrosine-overproducing yeast platform using targeted metabolomics.

Background: L-tyrosine is a common precursor for a wide range of valuable secondary metabolites, including benzylisoquinoline alkaloids (BIAs) and many polyketides. An industrially tractable yeast strain optimized for production of L-tyrosine could serve as a platform for the development of BIA and polyketide cell factories. This study applied a targeted metabolomics approach to evaluate metabolic engineering strategies to increase the availability of intracellular L-tyrosine in the yeast Saccharomyces cerevisiae CEN.

Linking RNA measurements and proteomics with genome-scale models.

Genome-scale metabolic models (GMMs) have been recognized as being powerful tools for capturing system-wide metabolic phenomena and connecting those phenomena to underlying genetic and regulatory changes. By formalizing and codifying the relationship between the levels of gene expression, protein concentration, and reaction flux, metabolic models are able to translate changes in gene expression to their effects on the metabolic network. A number of methods are then available to interpret how those changes are manifest in the metabolic flux distribution.

Applications of systems biology towards microbial fuel production.

Harnessing the immense natural diversity of biological functions for economical production of fuel has enormous potential benefits. Inevitably, however, the native capabilities for any given organism must be modified to increase the productivity or efficiency of a biofuel bioprocess. From a broad perspective, the challenge is to sufficiently understand the details of cellular functionality to be able to prospectively predict and modify the cellular function of a microorganism.

Genome-scale metabolic model integrated with RNAseq data to identify metabolic states of Clostridium thermocellum.

Constraint-based genome-scale metabolic models are becoming an established tool for using genomic and biochemical information to predict cellular phenotypes. While these models provide quantitative predictions for individual reactions and are readily scalable for any biological system, they have inherent limitations. Using current methods, it is difficult to computationally elucidate a specific network state that directly depicts an in vivo state, especially in the instances where the organism might be functionally in a suboptimal state.

Exploring biodiversity for cellulosic biofuel production.

Industrial production of solvents such as EtOH and BuOH from cellulosic biomass has the potential to provide a sustainable energy source that is relatively cheap, abundant, and environmentally sound, but currently production costs are driven up by expensive enzymes, which are necessary to degrade cellulose into fermentable sugars. These costs could be significantly reduced if a microorganism could be engineered to efficiently and quickly convert cellulosic biomass directly to product in a one-step process. There is a large amount of biodiversity in the number of existing microorganisms that naturally possess the enzymes necessary to convert cellulose to usable sugars, and many of these microorganisms can directly ferment sugars to EtOH or other solvents.

Genome-scale metabolic analysis of Clostridium thermocellum for bioethanol production.

Background: Microorganisms possess diverse metabolic capabilities that can potentially be leveraged for efficient production of biofuels. Clostridium thermocellum (ATCC 27405) is a thermophilic anaerobe that is both cellulolytic and ethanologenic, meaning that it can directly use the plant sugar, cellulose, and biochemically convert it to ethanol. A major challenge in using microorganisms for chemical production is the need to modify the organism to increase production efficiency.