Chassis engineering for microbial production of chemicals: from natural microbes to synthetic organisms.

Chassis provides a setting for the expression of heterologous pathway genes, which often requires extensive engineering to achieve complete functions. Traditionally, chassis engineering relies on gene deletion/overexpression for the regulation of precursor/cofactor supply and product transportation, which has generated thousands of high-performance strains. With the development of synthetic biology, chassis modifications have expanded to the synthesis of artificial cellular machineries, creating synthetic cells for the biosynthesis of bioproducts. In this review, we will discuss the development of chassis engineering technologies, termed the first-generation and second-generation technologies, and their applications in the creation of chassis for the production of valued-added chemicals, with an emphasis on synthetic chassis and their applications and potential. The development of chassis engineering technologies will advance rational design and construction of customized chassis for the manufacturing of target bioproducts.

[1]  Timothy B. Stockwell,et al.  Complete Chemical Synthesis, Assembly, and Cloning of a Mycoplasma genitalium Genome , 2008, Science.

[2]  Haoran Zhang,et al.  Modular co-culture engineering, a new approach for metabolic engineering. , 2016, Metabolic engineering.

[3]  Yingjin Yuan,et al.  Engineering Yarrowia lipolytica for Campesterol Overproduction , 2016, PloS one.

[4]  Yanli Qi,et al.  Engineering microbial membranes to increase stress tolerance of industrial strains. , 2019, Metabolic engineering.

[5]  Judy Qiu,et al.  Total Synthesis of a Functional Designer Eukaryotic Chromosome , 2014, Science.

[6]  G. Stephanopoulos,et al.  Improving fatty acids production by engineering dynamic pathway regulation and metabolic control , 2014, Proceedings of the National Academy of Sciences.

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

[8]  Di Liu,et al.  Dynamic metabolic control: towards precision engineering of metabolism , 2018, Journal of Industrial Microbiology & Biotechnology.

[9]  B. Hamberger,et al.  Metabolic Engineering of Synechocystis sp. PCC 6803 for Production of the Plant Diterpenoid Manoyl Oxide , 2015, ACS synthetic biology.

[10]  Mark P. Styczynski,et al.  Precision metabolic engineering: The design of responsive, selective, and controllable metabolic systems. , 2015, Metabolic engineering.

[11]  P. Wittung-Stafshede,et al.  Mirror‐Image 5S Ribonucleoprotein Complexes , 2019, Angewandte Chemie.

[12]  Jee Loon Foo,et al.  Synthetic biology toolkits and applications in Saccharomyces cerevisiae. , 2018, Biotechnology advances.

[13]  Guocheng Du,et al.  Modular pathway engineering of key carbon‐precursor supply‐pathways for improved N‐acetylneuraminic acid production in Bacillus subtilis , 2018, Biotechnology and bioengineering.

[14]  Huimin Zhao,et al.  Recent advances in metabolic engineering of Saccharomyces cerevisiae: New tools and their applications. , 2018, Metabolic engineering.

[15]  M. Bott,et al.  Construction of a Corynebacterium glutamicum platform strain for the production of stilbenes and (2S)-flavanones. , 2016, Metabolic engineering.

[16]  Guoqiang Chen,et al.  Synthetic Biology and Genome-Editing Tools for Improving PHA Metabolic Engineering. , 2019, Trends in biotechnology.

[17]  Huifeng Jiang,et al.  Engineering microbial cell factories for the production of plant natural products: from design principles to industrial-scale production , 2017, Microbial Cell Factories.

[18]  Y. Wang,et al.  Metabolic engineering of Saccharomyces cerevisiae for 7-dehydrocholesterol overproduction , 2018, Biotechnology for Biofuels.

[19]  Erik D. Carlson,et al.  Engineered ribosomes with tethered subunits for expanding biological function , 2019, Nature Communications.

[20]  Feng Gao,et al.  Bug mapping and fitness testing of chemically synthesized chromosome X , 2017, Science.

[21]  Byung-Kwan Cho,et al.  Minimal genome: Worthwhile or worthless efforts toward being smaller? , 2016, Biotechnology journal.

[22]  T. Tan,et al.  Cofactor engineering for more efficient production of chemicals and biofuels. , 2017, Biotechnology advances.

[23]  H. Alper,et al.  Synthetic Biology for Specialty Chemicals. , 2015, Annual review of chemical and biomolecular engineering.

[24]  G. Stephanopoulos,et al.  Efflux transporter engineering markedly improves amorphadiene production in Escherichia coli , 2016, Biotechnology and bioengineering.

[25]  Lei Liu,et al.  A synthetic molecular system capable of mirror-image genetic replication and transcription. , 2016, Nature chemistry.

[26]  Thomas H Segall-Shapiro,et al.  Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome , 2010, Science.

[27]  G. Stephanopoulos,et al.  Metabolic engineering in the host Yarrowia lipolytica. , 2018, Metabolic engineering.

[28]  Sang Yup Lee,et al.  Systems Metabolic Engineering Strategies: Integrating Systems and Synthetic Biology with Metabolic Engineering. , 2019, Trends in biotechnology.

[29]  Rodrigo Ledesma-Amaro,et al.  Microbial Chassis Development for Natural Product Biosynthesis. , 2020, Trends in biotechnology.

[30]  Manuel A. S. Santos,et al.  Non-Standard Genetic Codes Define New Concepts for Protein Engineering , 2015, Life.

[31]  Jason W. Chin,et al.  Expanding and reprogramming the genetic code , 2017, Nature.

[32]  Jianhui Gong,et al.  Engineering the ribosomal DNA in a megabase synthetic chromosome , 2017, Science.

[33]  Shunji Takahashi,et al.  Development of a Terpenoid-Production Platform in Streptomyces reveromyceticus SN-593. , 2017, ACS synthetic biology.

[34]  Xueli Zhang,et al.  Engineering an Artificial Membrane Vesicle Trafficking System (AMVTS) for the Excretion of β-Carotene in Escherichia coli. , 2019, ACS synthetic biology.

[35]  Thomas Lavergne,et al.  A Semi-Synthetic Organism with an Expanded Genetic Alphabet , 2014, Nature.

[36]  D. G. Gibson,et al.  Design and synthesis of a minimal bacterial genome , 2016, Science.

[37]  M. Moo-young,et al.  Metabolic engineering to enhance heterologous production of hyaluronic acid in Bacillus subtilis. , 2018, Metabolic engineering.

[38]  B A Blount,et al.  Rapid host strain improvement by in vivo rearrangement of a synthetic yeast chromosome , 2018, Nature Communications.

[39]  Yun Wang,et al.  Rapid pathway prototyping and engineering using in vitro and in vivo synthetic genome SCRaMbLE-in methods , 2018, Nature Communications.

[40]  M. Koffas,et al.  Optimizing oleaginous yeast cell factories for flavonoids and hydroxylated flavonoids biosynthesis. , 2019, ACS synthetic biology.

[41]  Yan Wang,et al.  “Perfect” designer chromosome V and behavior of a ring derivative , 2017, Science.

[42]  Akihiko Kondo,et al.  Engineering metabolic pathways in Escherichia coli for constructing a "microbial chassis" for biochemical production. , 2017, Bioresource technology.

[43]  Jianhui Gong,et al.  Deep functional analysis of synII, a 770-kilobase synthetic yeast chromosome , 2017, Science.

[44]  Yingjin Yuan,et al.  SCRaMbLE generates evolved yeasts with increased alkali tolerance , 2019, Microbial Cell Factories.

[45]  J. Nielsen,et al.  DCEO Biotechnology: Tools To Design, Construct, Evaluate, and Optimize the Metabolic Pathway for Biosynthesis of Chemicals. , 2018, Chemical reviews.

[46]  Peng Xu,et al.  Engineering Yarrowia lipolytica as a platform for synthesis of drop-in transportation fuels and oleochemicals , 2016, Proceedings of the National Academy of Sciences.

[47]  Transporter and its engineering for secondary metabolites , 2016, Applied Microbiology and Biotechnology.

[48]  P. Jensen,et al.  Metabolic engineering of Synechocystis sp. PCC 6803 for the production of aromatic amino acids and derived phenylpropanoids. , 2019, Metabolic engineering.

[49]  T. Ellis,et al.  Improved betulinic acid biosynthesis using synthetic yeast chromosome recombination and semi-automated rapid LC-MS screening , 2020, Nature Communications.

[50]  Mattheos A. G. Koffas,et al.  Metabolic engineering of Corynebacterium glutamicum for anthocyanin production , 2018, Microbial Cell Factories.

[51]  Aaron W Feldman,et al.  New codons for efficient production of unnatural proteins in a semi-synthetic organism , 2020, Nature Chemical Biology.

[52]  Yong Wang,et al.  Production of plant-specific flavones baicalein and scutellarein in an engineered E. coli from available phenylalanine and tyrosine. , 2019, Metabolic engineering.

[53]  Ying Wang,et al.  Chassis and key enzymes engineering for monoterpenes production. , 2017, Biotechnology advances.

[54]  K. Fan,et al.  Heterologous production of chlortetracycline in an industrial grade Streptomyces rimosus host , 2019, Applied Microbiology and Biotechnology.

[55]  Pablo I. Nikel,et al.  Chasing bacterial chassis for metabolic engineering: a perspective review from classical to non‐traditional microorganisms , 2018, Microbial biotechnology.

[56]  Julius Fredens,et al.  Total synthesis of Escherichia coli with a recoded genome , 2019, Nature.

[57]  Ying Wang,et al.  Manipulation of GES and ERG20 for geraniol overproduction in Saccharomyces cerevisiae. , 2017, Metabolic engineering.

[58]  Qipeng Yuan,et al.  Targeting metabolic driving and intermediate influx in lysine catabolism for high-level glutarate production , 2019, Nature Communications.

[59]  Michael C. Jewett,et al.  Protein synthesis by ribosomes with tethered subunits , 2015, Nature.

[60]  H. K. Dai,et al.  Synthesis, debugging, and effects of synthetic chromosome consolidation: synVI and beyond , 2017, Science.