title: Production of bulk chemicals via novel metabolic pathways in microorganisms.
abstract: Metabolic engineering has been playing important roles in developing high performance microorganisms capable of producing various chemicals and materials from renewable biomass in a sustainable manner. Synthetic and systems biology are also contributing significantly to the creation of novel pathways and the whole cell-wide optimization of metabolic performance, respectively. In order to expand the spectrum of chemicals that can be produced biotechnologically, it is necessary to broaden the metabolic capacities of microorganisms. Expanding the metabolic pathways for biosynthesizing the target chemicals requires not only the enumeration of a series of known enzymes, but also the identification of biochemical gaps whose corresponding enzymes might not actually exist in nature; this issue is the focus of this paper. First, pathway prediction tools, effectively combining reactions that lead to the production of a target chemical, are analyzed in terms of logics representing chemical information, and designing and ranking the proposed metabolic pathways. Then, several approaches for potentially filling in the gaps of the novel metabolic pathway are suggested along with relevant examples, including the use of promiscuous enzymes that flexibly utilize different substrates, design of novel enzymes for non-natural reactions, and exploration of hypothetical proteins. Finally, strain optimization by systems metabolic engineering in the context of novel metabolic pathways constructed is briefly described. It is hoped that this review paper will provide logical ways of efficiently utilizing 'big' biological data to design and develop novel metabolic pathways for the production of various bulk chemicals that are currently produced from fossil resources.
authors.affiliation: Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 program), Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea.
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Shin
authors.forename: Hyun Uk
authors.initials: HU
authors.lastname: Kim
authors.forename: Dong In
authors.initials: DI
authors.lastname: Kim
authors.forename: Sang Yup
authors.initials: SY
authors.lastname: Lee
mesh_terms: D001419:Bacteria / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D001709:Biotechnology; D019295:Computational Biology; D006801:Humans; D060847:Metabolic Engineering; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D058615:Synthetic Biology; D049490:Systems Biology
keywords: 1,4-BDO; 1,4-butanediol; 2-keto-acid decarboxylase; 3-hydroxypropionic acid; 3HP; 4-hydroxybutyryl-CoA; 4HB-CoA; ADH; BEM; BNICE; Biochemical Network Integrated Computational Explorer; Bulk chemicals; De novo pathway design; EC; Enzyme Commission; Enzyme modification; GOLD; Genome mining; Genomes OnLine Database; KDC; KEGG; Kyoto Encyclopedia of Genes and Genomes; Metabolic engineering; PHA; Pathway prediction; Promiscuous enzyme; SMILES; Strain optimization; Synthetic biology; UM-BBD; University of Minnesota Biocatalysis/Biodegradation Database; alcohol dehydrogenase; bond and electron matrix; polyhydroxyalkanoate; simplified molecular-input line-entry systems