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Yim H.,Genomatica | Haselbeck R.,Genomatica | Niu W.,Genomatica | Pujol-Baxley C.,Genomatica | And 14 more authors.
Nature Chemical Biology | Year: 2011

1,4-Butanediol (BDO) is an important commodity chemical used to manufacture over 2.5 million tons annually of valuable polymers, and it is currently produced exclusively through feedstocks derived from oil and natural gas. Herein we report what are to our knowledge the first direct biocatalytic routes to BDO from renewable carbohydrate feedstocks, leading to a strain of Escherichia coli capable of producing 18 g l 1 of this highly reduced, non-natural chemical. A pathway-identification algorithm elucidated multiple pathways for the biosynthesis of BDO from common metabolic intermediates. Guided by a genome-scale metabolic model, we engineered the E. coli host to enhance anaerobic operation of the oxidative tricarboxylic acid cycle, thereby generating reducing power to drive the BDO pathway. The organism produced BDO from glucose, xylose, sucrose and biomass-derived mixed sugar streams. This work demonstrates a systems-based metabolic engineering approach to strain design and development that can enable new bioprocesses for commodity chemicals that are not naturally produced by living cells. © 2011 Nature America, Inc. All rights reserved.

Kim Y.,Korea Advanced Institute of Science and Technology | Jeong H.,Korea Advanced Institute of Science and Technology | Jeong H.,Institute for the BioCentury
Physical Review E - Statistical, Nonlinear, and Soft Matter Physics | Year: 2011

Community structure exists in many real-world networks and has been reported being related to several functional properties of the networks. The conventional approach was partitioning nodes into communities, while some recent studies start partitioning links instead of nodes to find overlapping communities of nodes efficiently. We extended the map equation method, which was originally developed for node communities, to find link communities in networks. This method is tested on various kinds of networks and compared with the metadata of the networks, and the results show that our method can identify the overlapping role of nodes effectively. The advantage of this method is that the node community scheme and link community scheme can be compared quantitatively by measuring the unknown information left in the networks besides the community structure. It can be used to decide quantitatively whether or not the link community scheme should be used instead of the node community scheme. Furthermore, this method can be easily extended to the directed and weighted networks since it is based on the random walk. © 2011 American Physical Society.

Malaviya A.,Institute for the BioCentury | Jang Y.-S.,Institute for the BioCentury | Lee S.Y.,Institute for the BioCentury | Lee S.Y.,KAIST
Applied Microbiology and Biotechnology | Year: 2012

Butanol, a four-carbon primary alcohol (C 4H 10O), is an important industrial chemical and has a good potential to be used as a superior biofuel. Bio-based production of butanol from renewable feedstock is a promising and sustainable alternative to substitute petroleum-based fuels. Here, we report the development of a process for butanol production from glycerol, which is abundantly available as a byproduct of biodiesel production. First, a hyper butanol producing strain of Clostridium pasteurianum was isolated by chemical mutagenesis. The best mutant strain, C. pasteurianum MBEL-GLY2, was able to produce 10.8 gl -1 butanol from 80 gl -1 glycerol as compared to 7.6 gl -1 butanol produced by the parent strain. Next, the process parameters were optimized to maximize butanol production from glycerol. Under the optimized batch condition, the butanol concentration, yield, and productivity of 17.8 gl -1, 0.30 gg -1, and 0.43 gl -1 h -1 could be achieved. Finally, continuous fermentation of C. pasteurianum MBEL-GLY2 with cell recycling was carried out using glycerol as a major carbon source at several different dilution rates. The continuous fermentation was run for 710 h without strain degeneration. The acetone-butanol-ethanol productivity and the butanol productivity of 8.3 and 7.8 gl -1 h -1, respectively, could be achieved at the dilution rate of 0.9 h -1. This study reports continuous production of butanol with reduced byproducts formation from glycerol using C. pasteurianum, and thus could help design a bioprocess for the improved production of butanol. © 2011 Springer-Verlag.

Ahn J.-H.,Institute for the BioCentury | Choi S.-J.,Institute for the BioCentury | Han J.-W.,Institute for the BioCentury | Park T.J.,Institute for the BioCentury | And 4 more authors.
Nano Letters | Year: 2010

A silicon nanowire field effect transistor (FET) straddled by the double-gate was demonstrated for biosensor application. The separated double-gates, G1 (primary) and G2 (secondary), allow independent voltage control to modulate channel potential. Therefore, the detection sensitivity was enhanced by the use of G2. By applying weakly positive bias to G2, the sensing window was significantly broadened compared to the case of employing G1 only, which is nominally used in conventional nanowire FET-based biosensors. The charge effect arising from biomolecules was also analyzed. Double-gate nanowire FET can pave the way for an electrically working biosensor without a labeling process. © 2010 American Chemical Society.

Jung Y.K.,Institute for the BioCentury | Kim T.Y.,Institute for the BioCentury | Park S.J.,LG Corp | Lee S.Y.,Institute for the BioCentury | Lee S.Y.,Brain Bio
Biotechnology and Bioengineering | Year: 2010

Polylactic acid (PLA) is a promising biomass-derived polymer, but is currently synthesized by a two-step process: fermentative production of lactic acid followed by chemical polymerization. Here we report production of PLA homopolymer and its copolymer, poly(3-hydroxybutyrate-co-lactate), P(3HB-co-LA), by direct fermentation of metabolically engineered Escherichia coli. As shown in an accompanying paper, introduction of the heterologous metabolic pathways involving engineered propionate CoA-transferase and polyhydroxyalkanoate (PHA) synthase for the efficient generation of lactyl-CoA and incorporation of lactyl-CoA into the polymer, respectively, allowed synthesis of PLA and P(3HB-co-LA) in E. coli, but at relatively low efficiency. In this study, the metabolic pathways of E. coli were further engineered by knocking out the ackA, ppc, and adhE genes and by replacing the promoters of the ldhA and acs genes with the trc promoter based on in silico genome-scale metabolic flux analysis in addition to rational approach. Using this engineered strain, PLA homopolymer could be produced up to 11 wt% from glucose. Also, P(3HB-co-LA) copolymers containing 55-86 mol% lactate could be produced up to 56 wt% from glucose and 3HB. P(3HB-co-LA) copolymers containing up to 70 mol% lactate could be produced to 46 wt% from glucose alone by introducing the Cupriavidus necator β-ketothiolase and acetoacetyl-CoA reductase genes. Thus, the strategy of combined metabolic engineering and enzyme engineering allowed efficient bio-based one-step production of PLA and its copolymers. This strategy should be generally useful for developing other engineered organisms capable of producing various unnatural polymers by direct fermentation from renewable resources. © 2009 Wiley Periodicals, Inc.

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