Rewriting the Metabolic Blueprint: Advances in Pathway Diversification in Microorganisms

Living organisms have evolved over millions of years to fine tune their metabolism to create efficient pathways for producing metabolites necessary for their survival. Advancement in the field of synthetic biology has enabled the exploitation of these metabolic pathways for the production of desired compounds by creating microbial cell factories through metabolic engineering, thus providing sustainable routes to obtain value-added chemicals. Following the past success in metabolic engineering, there is increasing interest in diversifying natural metabolic pathways to construct non-natural biosynthesis routes, thereby creating possibilities for producing novel valuable compounds that are non-natural or without elucidated biosynthesis pathways. Thus, the range of chemicals that can be produced by biological systems can be expanded to meet the demands of industries for compounds such as plastic precursors and new antibiotics, most of which can only be obtained through chemical synthesis currently. Herein, we review and discuss novel strategies that have been developed to rewrite natural metabolic blueprints in a bid to broaden the chemical repertoire achievable in microorganisms. This review aims to provide insights on recent approaches taken to open new avenues for achieving biochemical production that are beyond currently available inventions.

[1]  L. Heide,et al.  An artificial pathway to 3,4-dihydroxybenzoic acid allows generation of new aminocoumarin antibiotic recognized by catechol transporters of E. coli. , 2011, Chemistry & biology.

[2]  Michael A Fischbach,et al.  Computational approaches to natural product discovery. , 2015, Nature chemical biology.

[3]  Niying Chua,et al.  Engineering a riboswitch-based genetic platform for the self-directed evolution of acid-tolerant phenotypes , 2017, Nature Communications.

[4]  Frances H. Arnold,et al.  Enantioselective Imidation of Sulfides via Enzyme-Catalyzed Intermolecular Nitrogen-Atom Transfer , 2014, Journal of the American Chemical Society.

[5]  Yinjie J. Tang,et al.  Synthetic biology for manufacturing chemicals: constraints drive the use of non-conventional microbial platforms , 2017, Applied Microbiology and Biotechnology.

[6]  L. Wackett.  An annotated selection of World Wide Web sites relevant to the topics in Microbial Biotechnology , 2013, Microbial biotechnology.

[7]  J. Foo,et al.  Engineering Saccharomyces cerevisiae to produce odd chain‐length fatty alcohols , 2016, Biotechnology and bioengineering.

[8]  Benjamin W. Thuronyi,et al.  Expanding the Fluorine Chemistry of Living Systems Using Engineered Polyketide Synthase Pathways , 2013, Science.

[9]  Richard A. Lewis,et al.  Introduction of a non-natural amino acid into a nonribosomal peptide antibiotic by modification of adenylation domain specificity. , 2012, Angewandte Chemie.

[10]  Aaron W Feldman,et al.  A Semi-Synthetic Organism that Stores and Retrieves Increased Genetic Information , 2017, Nature.

[11]  James C. Liao,et al.  Directed Evolution of Methanococcus jannaschii Citramalate Synthase for Biosynthesis of 1-Propanol and 1-Butanol by Escherichia coli , 2008, Applied and Environmental Microbiology.

[12]  K. Shanmugam,et al.  Evolution of D-lactate dehydrogenase activity from glycerol dehydrogenase and its utility for D-lactate production from lignocellulose , 2011, Proceedings of the National Academy of Sciences.

[13]  R. Gupta.  Recent advances in enzyme promiscuity , 2016 .

[14]  Jay. D. Keasling,et al.  Metabolic engineering of Escherichia coli for the biosynthesis of 2-pyrrolidone , 2015, Metabolic engineering communications.

[15]  Chaitan Khosla,et al.  Improved Precursor Directed Biosynthesis in E. coli via Directed Evolution , 2010, The Journal of Antibiotics.

[16]  J. Krömer,et al.  Metabolic Engineering of Pseudomonas putida KT2440 for the Production of para-Hydroxy Benzoic Acid , 2016, Front. Bioeng. Biotechnol..

[17]  Magali Remaud-Siméon,et al.  Construction of a synthetic metabolic pathway for biosynthesis of the non-natural methionine precursor 2,4-dihydroxybutyric acid , 2017, Nature Communications.

[18]  Ronan M. T. Fleming,et al.  fastGapFill: efficient gap filling in metabolic networks , 2014, Bioinform..

[19]  Jee Loon Foo,et al.  The imminent role of protein engineering in synthetic biology. , 2012, Biotechnology advances.

[20]  Frances H. Arnold,et al.  Genetically programmed chiral organoborane synthesis , 2017, Nature.

[21]  B. Pfeifer,et al.  Complete biosynthesis of erythromycin A and designed analogs using E. coli as a heterologous host. , 2010, Chemistry & biology.

[22]  John A Gerlt,et al.  Genomic Enzymology: Web Tools for Leveraging Protein Family Sequence–Function Space and Genome Context to Discover Novel Functions , 2017, Biochemistry.

[23]  Q. Zhu,et al.  Metabolic engineering of Yarrowia lipolytica for industrial applications. , 2015, Current opinion in biotechnology.

[24]  F. Arnold,et al.  Directed evolution of cytochrome c for carbon–silicon bond formation: Bringing silicon to life , 2016, Science.

[25]  Jianzhuang Yao,et al.  Substrate-Assisted Catalysis in the Reaction Catalyzed by Salicylic Acid Binding Protein 2 (SABP2), a Potential Mechanism of Substrate Discrimination for Some Promiscuous Enzymes. , 2015, Biochemistry.

[26]  J. Hopfield,et al.  From molecular to modular cell biology , 1999, Nature.

[27]  N. Kelleher,et al.  Directed evolution of the nonribosomal peptide synthetase AdmK generates new andrimid derivatives in vivo. , 2011, Chemistry & biology.

[28]  A. Xiao,et al.  Metabolic engineering of Escherichia coli for the biosynthesis of various phenylpropanoid derivatives. , 2015, Metabolic engineering.

[29]  C. Smolke,et al.  Complete biosynthesis of opioids in yeast , 2015, Science.

[30]  Yinjie J. Tang,et al.  Facilitate Collaborations among Synthetic Biology, Metabolic Engineering and Machine Learning , 2016 .

[31]  Dirk Inzé,et al.  Plant cell factories in the post-genomic era: new ways to produce designer secondary metabolites. , 2004, Trends in plant science.

[32]  P. Babbitt,et al.  Enzyme (re)design: lessons from natural evolution and computation. , 2009, Current opinion in chemical biology.

[33]  Aldo R. Boccaccini,et al.  Engineering of Metabolic Pathways by Artificial Enzyme Channels , 2015, Front. Bioeng. Biotechnol..

[34]  Santiago Comba,et al.  Expanding the chemical diversity of natural esters by engineering a polyketide-derived pathway into Escherichia coli. , 2014, Metabolic engineering.

[35]  Jay D Keasling,et al.  Multiplex metabolic pathway engineering using CRISPR/Cas9 in Saccharomyces cerevisiae. , 2015, Metabolic engineering.

[36]  Enrique Blanco,et al.  Computational gene annotation in new genome assemblies using GeneID. , 2009, Methods in molecular biology.

[37]  K. Ishida,et al.  Rational design of modular polyketide synthases: morphing the aureothin pathway into a luteoreticulin assembly line. , 2014, Angewandte Chemie.

[38]  Deepak Chandran,et al.  Computational tools for metabolic engineering. , 2012, Metabolic engineering.

[39]  J. Gerlt.  Tools and strategies for discovering novel enzymes and metabolic pathways , 2016 .

[40]  A. Chaudhary,et al.  Enhanced production of nargenicin A1 and creation of a novel derivative using a synthetic biology platform , 2016, Applied Microbiology and Biotechnology.

[41]  E. Balskus,et al.  Opportunities for merging chemical and biological synthesis. , 2014, Current opinion in biotechnology.

[42]  Qipeng Yuan,et al.  High-level De novo biosynthesis of arbutin in engineered Escherichia coli. , 2017, Metabolic engineering.

[43]  Jef Boeke,et al.  The Saccharomyces cerevisiae SCRaMbLE system and genome minimization , 2012, Bioengineered bugs.

[44]  Sung-Hee Park,et al.  Deoxysugar pathway interchange for erythromycin analogues heterologously produced through Escherichia coli. , 2013, Metabolic engineering.

[45]  J. Qiao,et al.  Metabolic engineering of Escherichia coli for production of salvianic acid A via an artificial biosynthetic pathway. , 2013, Metabolic engineering.

[46]  Yi Tang,et al.  Heterologous expression and manipulation of three tetracycline biosynthetic pathways. , 2012, Angewandte Chemie.

[47]  Micheal C. Wilson,et al.  Beyond ethylmalonyl-CoA: the functional role of crotonyl-CoA carboxylase/reductase homologs in expanding polyketide diversity. , 2012, Natural product reports.

[48]  V. Lorenzo,et al.  Biotechnological domestication of pseudomonads using synthetic biology , 2014, Nature Reviews Microbiology.

[49]  U. Bornscheuer,et al.  Microbial Synthesis of Medium-Chain α,ω-Dicarboxylic Acids and ω-Aminocarboxylic Acids from Renewable Long-Chain Fatty Acids , 2014 .

[50]  Yinjie J. Tang,et al.  Metabolic Burden: Cornerstones in Synthetic Biology and Metabolic Engineering Applications. , 2016, Trends in biotechnology.

[51]  Yitzhak Apeloig,et al.  The chemistry of organic silicon compounds , 1989 .

[52]  Pablo Carbonell,et al.  Validation of RetroPath, a computer-aided design tool for metabolic pathway engineering. , 2014, Biotechnology journal.

[53]  M. Marsden,et al.  Designed, Synthetically Accessible Bryostatin Analogues Potently Induce Activation of Latent HIV Reservoirs in vitro , 2012, Nature chemistry.

[54]  Ryohei Kato,et al.  Synthesis of unnatural alkaloid scaffolds by exploiting plant polyketide synthase , 2011, Proceedings of the National Academy of Sciences.

[55]  B. Pfeifer,et al.  Metabolic and pathway engineering to influence native and altered erythromycin production through E. coli. , 2013, Metabolic engineering.

[56]  Hyun Uk Kim,et al.  Production of bulk chemicals via novel metabolic pathways in microorganisms. , 2013, Biotechnology advances.

[57]  Chaitan Khosla,et al.  Engineering the acyltransferase substrate specificity of assembly line polyketide synthases , 2013, Journal of The Royal Society Interface.

[58]  Alan L Harvey,et al.  Natural products in drug discovery. , 2008, Drug discovery today.

[59]  Wenjun Zhang,et al.  De novo biosynthesis of terminal alkyne-labeled natural products. , 2015, Nature chemical biology.

[60]  M. Takemura,et al.  4-Ketozeinoxanthin, a novel carotenoid produced in Escherichia coli through metabolic engineering using carotenogenic genes of bacterium and liverwort , 2014 .

[61]  Yixin Chen,et al.  BoostGAPFILL: improving the fidelity of metabolic network reconstructions through integrated constraint and pattern‐based methods , 2016, Bioinform..

[62]  Pablo Carbonell,et al.  Retropath: automated pipeline for embedded metabolic circuits. , 2014, ACS synthetic biology.

[63]  Frances H. Arnold,et al.  A Serine-Substituted P450 Catalyzes Highly Efficient Carbene Transfer to Olefins In Vivo , 2013, Nature chemical biology.

[64]  C. Khosla.  Quo vadis, enzymology? , 2015, Nature chemical biology.

[65]  S. Lee,et al.  Systems strategies for developing industrial microbial strains , 2015, Nature Biotechnology.

[66]  D. Dhakal,et al.  Marine Rare Actinobacteria: Isolation, Characterization, and Strategies for Harnessing Bioactive Compounds , 2017, Front. Microbiol..

[67]  Frances H. Arnold,et al.  Enantioselective Enzyme-Catalyzed Aziridination Enabled by Active-Site Evolution of a Cytochrome P450 , 2015, ACS central science.