Importance of systems biology in engineering microbes for biofuel production

Abstract

Microorganisms have been rich sources for natural products, some of which have found use as fuels, commodity chemicals, specialty chemicals, polymers, and drugs, to name a few. The recent interest in production of transportation fuels from renewable resources has catalyzed numerous research endeavors that focus on developing microbial systems for production of such natural products. Eliminating bottlenecks in microbial metabolic pathways and alleviating the stresses due to production of these chemicals are crucial in the generation of robust and efficient production hosts. The use of systemslevel studies makes it possible to comprehensively understand the impact of pathway engineering within the context of the entire host metabolism, to diagnose stresses due to product synthesis, and provides the rationale to cost-effectively engineer optimal industrial microorganisms.

Metabolic engineering of Escherichia coli for the production of putrescine: A four carbon diamine

“…Recently, several examples of systems metabolic engineering, which is metabolic engineering performed with the consideration of the entire metabolic network and complex regulatory circuits in an integrated manner, have appeared (Alper et al, 2006;Lee et al, 2005;Mukhopadhyay et al, 2008;. For instance, an E. coli L-valine overproducer was constructed by genome engineering combined with engineering the targets that were identified by transcriptome profiling and gene knockout simulation of the in silico genome-scale metabolic network .…”

Advanced biofuel production in microbes

“…Yet, it may be possible to achieve higher advanced biofuel titers by simultaneously modifying variables that, at first glance, appear further removed from the pathway. To identify these variables, we need a system-level understanding of microbial metabolism and the effects of fuel toxicity [59]. By taking advantage of functional genomic techniques to monitor thousands of parameters simultaneously, and by then integrating these system-wide data into models, we should be able to accurately represent a snapshot of the cell metabolism.…”

Metabolic engineering of microorganisms for biofuels production: from bugs to synthetic biology to fuels

“…The user-friendly hosts (Escherichia coli and Saccharomyces cerevisiae) that have well-character-ized genetics and the genetic tools [ 6,10] for manipulating them are good starting points for development as production platforms. Because these host organisms are also facultative anaerobes with fast growth rates, large-scale production processes can be relatively simple and economically viable [11][12][13].…”

“…The successful use of E. coli or S. cerevisiae to produce alternative biofuels will require a better understanding of their physiology under a variety of conditions and subsequent strain improvements [ 10]. Continuous advances in 'omics' technologies, computational systems biology, and synthetic biology make it possible to better understand and engineer fuel production hosts with desired phenotypes [6,14]. Route from sunlight to fuels.…”

“…Third, new biosynthetic pathways can be engineered to produce fossil-fuel replacements, including shortchain, branched-chain, and cyclic alcohols, alkanes, alkenes, esters and aromatics. The development of cost-effective and energy-efficient processes to convert lignocellulose into fuels is hampered by significant roadblocks, including the lack of genetic engineering tools for native producer organisms (non-model organ-isms), and difficulties in optimizing metabolic pathways and balancing the redox state in the engineered microbes [ 6]. Furthermore, production potentials are limited by the low activity of pathway enzymes and the inhibitory effect of fuels and byproducts from the upstream biomass processing steps on microorganisms responsible for producing fuels.…”