Software

Codon Optimization On-Line (COOL)
SynLinker


SynCTI’s Research Foci

Honey Comb

SynCTI aims to develop foundational science and technology that will enhance our capacity to engineer biological systems with complexity and functions to serve a myriad of biotechnological applications in areas of healthcare, energy and the environment. Our strategic research thrusts will provide tools and solutions to confront current bottlenecks in synthetic biology with key emphasis on the development of (i) chassis and vectors, (ii) parts and devices and (iii) testbeds.

Our team of devoted researchers is divided into closely integrated clusters focusing on six areas of research, namely, microbial bio-manufacturing, therapeutic cells, environment remediation, mammalian bio-production, cell-free and whole-cell biosensors, and synthetic genomics. Research development in SynCTI is accelerated by cutting edge technologies and resources available at the NUS Synthetic Biology Foundry.

Honey Comb


Synthetic Biology Foundry

NUS Synthetic Biology Foundry represents a hallmark of synthetic biology research in driving foundational science towards translational clinical and industrial biotechnology applications. Equipped with state-of-the-art robotic system that is interfaced with various high throughput analytical instruments, the Foundry enables systematic (re)designing, building, testing and learning of synthetic biological systems on a highly efficient, automated manufacturing platform. Working together with our Scientific and Industrial Advisory Boards, and collaborators from the Global Synthetic Biology Laboratory, we have developed the Foundry to meet the rigorous standards and technical needs of the synthetic biology community. By fostering advanced research through international collaborations, the Foundry aims to become a central hub for cutting-edge synthetic biology research in Asia.

Bio Foundry

 

Contemporary equipment available at the Foundary includes: flow cytometry analyzer, fluorescent activated cell sorter, gas chromatography mass spectrometers, liquid chromatography quadrupole-time-of-flight mass spectrometer, ultra-high performance liquid chromatography diode-array detectors, fast protein liquid chromatography, automated fluorescent microscope, condition-controlled bioreactors, robotic colony pickers and liquid handling robotics.

(Source: TK, SynCTI)


Bio-Manufacturing

Microorganisms have been used for decades in the production of fermented food and chemicals and as sources of antibiotics and enzymes. Microbial hosts are versatile platforms to produce valuable products from inexpensive renewable raw materials. These natural or synthetic products have numerous applications in the chemical, pharmaceutical, food and agriculture industries. Approval of the first clinical use of recombinant human insulin by the Food and Drug Administration in the early 1980’s inaugurated the production of recombinant pharmaceuticals for human use of which, by 2009, 48% were produced in microbial cells. Besides the clear economic impetus for the production of pharmaceuticals in microorganisms, pressing environment and energy security concerns have also driven an increasing interest in their use in the production of bio-derived fuel alternatives. Bio-manufacturing also present an advantage in the production of fine chemicals, such as amino acids, organic acids, flavors, fragrances and nutraceuticals, some of which are otherwise too complicated to be produced economically in other systems.

In SynCTI, our research aims to exploit recent advances in synthetic biology and utilize newly available tools in genetic, protein and metabolic engineering to construct and incorporate new biosynthetic or artificial metabolic pathways into microbes for the production of compounds with strong industrial relevance and potential. To further enhance productivity and yield of the microbial cell factories, we develop high throughput screening platforms that are used in combination with synthetic DNA libraries and directed evolution techniques to screen for robust engineered microbes that meet their intended purposes.

biomanufacturing

Early efforts in synthetic biology focused primarily on novel engineered systems in bacteria and lower eukaryotes. Today, increasingly advanced synthetic biology approaches are applied to mammalian cells enabling rational design in substantially more complex biological networks. Many basic genetic control elements that act on transcriptional, translational and posttranslational regulation have been well characterized and these are exploited to engineer higher-order, multicomponent gene circuitry that can drive predictable and controllable gene expression. Developments in mammalian synthetic biology is envisaged to pave the way for prospective clinical applications such as drug discovery, vaccine delivery and biopharmaceutical manufacturing in mammalian cells. In SynCTI, our research aims to engineer synthetic gene regulation into the design and control of Chinese hamster ovary (CHO) cells for the discovery and scale-up production of drug targets and novel therapeutic compounds.

Biotech 2014


Therapeutic Cells

The human body is home to a diverse community of symbiotic, commensal and pathogenic microorganisms, collectively known as microbiota. Disruption of the homeostatic relationship between microbiota and host, or dysbiosis, can result in maladies in human health ranging from metabolism to immunity. Cell-based therapeutics seek to leverage the intimate host-microbe associations as a platform technology to improve human health and treat diseases. Indeed, cell therapy is regarded as the fourth and final pillar of healthcare after pharmaceuticals, biologics and medical devices.

therapeuticcell

Early therapeutic approaches involved the manipulation of commensal microbial composition through diet and the use of antibiotics, probiotics and prebiotics. With the advent of new tools in synthetic biology, we envisage the next generation of cell-based therapeutics to involve engineering of the microbial genome (microbiome) to create recombinant microbes that are producers and targeted delivery vehicles of beneficial molecules that can alleviate metabolic disorders, or antimicrobials that can selectively eliminate deleterious microbes. Much of today’s research is focused on gut biota where the greatest abundance and diversity of microbes are found but scientific interest is steadily extending to other bodily niches, including the skin as well the oral, nasal and vaginal cavities for their immense therapeutic potential.

Deliberate modulation of microbiota-host metabolic and immune interactions remains a technically complex challenge that will require exquisite knowledge of microbial ecology and in-depth understanding of the cross-talk between host and microbiota. Our research group aims to elucidate the biological mechanisms behind microbiota-host interactions through bioprospecting and omic analyses of the human microbiota. Working synergistically with clinicians, immunologists and microbiologists from the NUS Synthetic Biology consortium, we ambition to reprogram the human microbiota into functional probiotics with prophylactic and therapeutic properties against human infectious diseases and immune and metabolic disorders, thereon translating microbiome therapeutics into real-world clinical applications.

Find Out More: hmpdacc.org


Environment Remediation

SynCTI Scientists

Microbe-metal interactions have been well documented in nature and the natural capability of microbes in metal biocatalysis has since been harnessed in industrial biotechnological processes such as the biomining of ores and the treatment of metal-contaminated wastewaters. In the face of a steady depletion of high grade ore reserves and growing concerns on environment degradation, microbial processes offers a economically viable and environmentally sustainable possibility of recovering valuable metals through the recycling of metal-laden leachate or solid waste otherwise deemed worthless.

The insatiable demand for electronics, exacerbated by their short life span, has resulted in the dire accumulation of end-of-life electrical and electronic products, or e-waste. Though mounting e-waste poses a major disposal challenge, it is potentially a secondary source for recovering precious metals such as platinum and gold. In contrast to current metal recycling processes, which are either energy intensive or have adverse environmental and human health impact, bioleaching using microorganisms presents a greener alternative in the recovery of precious metals from e-waste.

Our research aims to amalgamate synthetic biology with metallurgical principles to repurpose bioleaching microbes into practical biological lixiviants (i.e. solvents used in hydrometallurgy that selectively extracts metal from a source). Through genome editing and metabolic engineering, we work towards optimising lixiviant biosynthesis in the synthetic hosts, increasing metal recovery from the lixiviant medium as well as remediating excess lixiviants in the host systems. We envision that our research endeavours will culminate in the creation of novel metabolically-engineered microorganisms that can serve not only the recovery of commodity metals from e-waste on an industrial scale but also be deployed in the bioremediation of toxic metals from waste and landfills.


Biosensors

Organisms naturally monitor their environment and react accordingly. This innate ability to detect and sense has long been tapped by humans, such as the bygone use of canaries to detect poisonous gases in coal mines. With the advent of molecular biology techniques, it became possible to harness nature’s toolbox to develop synthetic monitoring systems known as biosensors. Biosensors are analytical devices encompassing a biological sensing element coupled to a physicochemcial transducer for the detection of target compounds. Conferring exquisite specificity and sensitivity, the biological entity includes enzymes, antibodies, receptor proteins, DNAs and even living cells.

Biosensors find application in medicine, process control, food and environmental monitoring, of which the estimated US$15 billion global market is driven largely by medical diagnostics, a result of an ever-increasing need for reliable diagnostic tools for the rise in chronic and infectious diseases. Emerging concerns on food safety and environmental contamination and the elevated threat of bioterrorism has also spurred the design of biosensors for the detection of a growing array of targets such as pesticides, heavy metals, organic pollutants, pathogens and toxins.

The building blocks to biosensors can be taken directly from natural systems, engineered from naturally occurring elements, or constructed entirely in vitro, aided by the rapidly advancing field of synthetic biology. Synthetic biology provides a rational framework for the modular design and reprogramming of genetic regulatory circuits into biosensors, opening the possibility of creating more sophisticated constructs for the development of multifarious affinity biosensors for complex diseases such as cancer. Armed with promising new tools in synthetic biology and improved materials from nanotechnology, our research group is working towards developing novel cell-based and cell-free biosensors built on both microbial and mammalian systems.


Synthetic Genomics

The idea of building whole genomes is one of the eagerly anticipated promises of synthetic biology. Whole-scale genome engineering has the potential to create designer cells tailor made to serve as novel platforms for biotechnology innovations and applications. The design and de novo synthesis of genomes nonetheless remains a technically daunting challenge.

syntheticyeastgenome

Years-long efforts by scientists to build a minimal cell, one with the least number of genes needed to sustain life, cumulated in the creation of the first synthetic organism with an artificial genome – Mycoplasma mycoides JCVI-syn1.0 in 2010. After three cycles of (re-)design, synthesis and testing, syn3.0 was unveiled in 2016 which, at 531 kbp, has a genome that is smaller than any autonomously replicating cell found in nature.
Inevitably, scientific breakthroughs in synthetic prokaryotic systems aspire parallel advancements in eukaryotes. Having come a long way from its primary use as a fermentation agent in brewing and baking, yeast is currently an essential part of the biotechnology industry with its widespread use for the production of food ingredients, pharmaceuticals, chemicals, and fuels. The first eukaryotic organism to have its full genome sequenced in 1996, yeast is also an important model organism for studying eukaryotic genetics and an ideal candidate to extend synthetic genomics beyond bacteria.

Synthetic Yeast 2.0

The Synthetic Yeast Genome Project (Sc2.0) is the world’s first synthetic eukaryotic genome project that aims to create a novel, rationalized version of the genome of the yeast species Saccharomyces cerevisiae. SynCTI is proud to be part of the international consortium embarked on the challenging but exciting task of building 16 designer synthetic chromosomes encompassing ~12 million base pairs of DNA. With each chromosome being synthesized simultaneously by research teams across the world, SynCTI joins leading academic and commercial institutions, including New York University, John Hopkins University, Tianjin University, Tsinghua University, University of Edinburgh, Imperial College London, MacQuarie University, Genscript and the Beijing Genomic Institute, in a truly global concerted effort for the advancement of synthetic genomics.

Aided by an array of genome editing and bioinformatics tools, our group will work to refactor the assigned yeast chromosome XV in abidance to the three core design principles: maintenance of wild-type phenotype and fitness, assurance of genomic stability and enhancement of genetic flexibility. The Sc2.0 project will ultimately yield a synthetic yeast equipped with novel functionalities that will not only be a boon for the direct interrogation of basic science questions but also present a novel platform to usher in breakthroughs in contemporary medical and industrial biotechnologies.

Find Out More > syntheticyeast.org

NUHS Summit Research Programme

Launched in October 2016 by the National University Health System (NUHS), the Summit Research Programme (SRP) is an initiative that seeks to achieve significant improvements in disease understanding and innovations in clinical practices that will improve healthcare and lead to societal benefits for Singapore. The SRP draws on the participation of academics and medical experts at the NUS Yong Loo Lin School of Medicine as well as clinician-scientists from NUHS to form collaborative research programmes to better understand and develop treatments to some of the most challenging medical and health issues.

The pioneering batch of SRPs focuses on 5 fields of interest:
> Cancer
> Cardiovascular Disease
> Metabolic Disease
> Tuberculosis
> Synthetic Biology

Headed by Associate Professor Matthew Chang, the SRP – Synthetic Biology aims to develop new prebiotics and therapeutic chemicals as well as to establish novel microbiome therapy for disease treatment. Driven by shared goals, SynCTI effectively engages with clinician-scientists under the NUHS SRP to advance the translation of synthetic biology research into potential clinical applications.

Find Out More > http://nusmedicine.nus.edu.sg/research-footer/summit-research-programmes


Publications

2017

Autoinducer sensing microarrays by reporter bacteria encapsulated in hybrid supramolecular-polysaccharide hydrogels

Li P, Dou XO, Müller M, Feng C, Chang MW, Frettlöh M, Schönherr H

Macromolecular Bioscience 1700176 (2017)

Encapsulation of Autoinducer Sensing Reporter Bacteria in Reinforced Alginate-based Microbeads

Li P, Müller M, Chang MW, Frettlöh M, Schönherr H.

ACS Appl Mater Interfaces (2017)

Engineering a riboswitch-based genetic platform for the self-directed evolution of acid-tolerant phenotypes

Pham HL, Wong A, Chua N, Teo WS, Yew WS, and Chang MW

Nature Communications (accepted) (2017)

Isolated Reporter Bacteria in Supramolecular Hydrogel Microwell Arrays

Li P, Dou XQ, Feng C, Müller M, Chang MW, Frettlöh M, Schönherr H

Langmuir (2017)

Designer probiotics for the prevention and treatment of human diseases

Chua KJ, Kwok WC, Aggarwal N, Sun T, Chang MW

Current Opinion in Chemical Biology 40:8-16 (2017)

Synthetic gene design using Codon Optimization On-Line (COOL)

Yu K, Ang KS, Lee DY

Methods in Molecular Biology 1472:13-34 (2017)

Engineered probiotic Escherichia coli can eliminate and prevent Pseudomonas aeruginosa infection in animal models

Hwang IY, Koh E, Wong CK, March JC, Bentley WE, Lee YS, Chang MW

Nature Communications In press (2017)

Applying the Design-Build-Test paradigm in microbiome engineering

Pham HL, Ho CL, Wong A, Lee YS, Chang MW

Current Opinion in Biotechnology 48:85-93 (2017)

The fungal mycobiome and interaction with gut bacteria in the host

Sam QH, Chang MW, Chai LYA

International Journal of Molecular Sciences 18:330-341 (2017)

Microbiome engineering: current applications and its future

Foo JL, Ling H, Lee YS, Chang MW

Biotechnology Journal 12:e1600099 (2017)


2016

Highly regio- and enantioselective multiple oxy- and amino-functionalizations of alkenes by modular cascade biocatalysis

Wu S, Zhou Y, Wang T, Too HP, Wang DIC, Li Z

Nature Communications 7:11917 (2016)

Cascade biocatalysis for sustainable asymmetric synthesis: from biobased I-phenylalanine to high-value chiral chemicals

Zhou Y, Wu S, Li Z

Angewandte Chemie 55:11647-11650 (2016)

Multi-omics data driven analysis establishes reference codon biases for synthetic gene design in microbial and mammalian cells

Ang KS, Kyriakopoulos S., Li W, Lee DY

Methods 102:26-35 (2016)

Codon optimization of Saccharomyces cerevisiae mating factor alpha prepro-leader to improve recombinant protein production in Pichia pastoris

Ahn J, Jang MJ, Ang KS, Lee H, Choi ES, Lee DY

Biotechnology Letters 38:2137-2143 (2016)

A genetic algorithm-based approach for pre-processing metabolomics and lipidomics LC-MS data

Yeo HC, Chung BKS, Chong W, Chin JX, Ang KS, Lakshmanan M, Ho YS, Lee DY

Metabolomics 12: 5 (2016)

Transcriptomics-based strain optimization tool for designing secondary metabolite overproducing strains of Streptomyces coelicolor

Kim M, Yi JS, Lakshmanan M, Lee DY, Kim BG

Biotechnology and Bioengineering 113:651-660 (2016)

Coordinate regulation of metabolite glycosylation and stress hormone biosynthesis by TT8 in Arabidopsis

Rai A, Umashankar S, Rai M, Lim BK, Aow JSB, Swarup S

Plant Physiology 171:2499-2515 (2016)

Flagellin FliC phosphorylation affects type 2 protease secretion and biofilm dispersal in Pseudomonas aeruginosa PAO1

Suriyanarayanan T, Periasamy S, Lin MH, Ishihama Y, Swarup S

PLoS One 11:e0164155 (2016)

Reprogrammable microbial cell-based therapeutics against antibiotic-resistant bacteria

Hwang IY, Koh E, Kim HR, Chang MW

Drug Resistance Updates 27:59-71 (2016)

Anti-virulent disruption of pathogenic biofilms using engineered quorum-quenching lactonases

Tay SB, Chow JY, Go M, Yew WS

Journal of Visualized Experiments 107:e53243 (2016)

Exploiting the biosynthetic potential of type III polyketide synthases

Lim YP, Go M, Yew WS

Molecules 21: 53-61 (2016)

A two-layer gene circuit for decoupling cell growth from metabolite production

Lo T, Chng SH, Teo WS, Cho HS, Chang MW

Cell Systems 3:133-143 (2016)

Metabolic engineering of Saccharomyces cerevisiae for the overproduction of short branched-chain fatty acids

Yu A, Pratomo NK, Foo JL, Leong SSJ, Chang MW

Metabolic Engineering 34:36-43 (2016)

Whole-cell biocatalytic and de novo production of alkanes from free fatty acids in Saccharomyces cerevisiae

Foo JL, Susanto AV, Keasling JD, Leong SSJ, Chang MW

Biotechnology and Bioengineering 114:232-237 (2016)

Genetic engineering of an unconventional yeast for renewable biofuel and biochemical production

Yu AQ, Pratomo N, Ng TK, Ling H, Cho HS, Leong SS, Chang MW

Journal of Visualized Experiments 115:e54371 (2016)

Synthetic biology in Asia: New kid on the block

Chang MW

ACS Synthetic Biology 5: 1182-1183 (2016)

Genome-scale metabolic modeling in silico analysis of lipid accumulating yeast Candida tropicalis for dicarboxylic acid production

Mishra P, Park GY, Lakshmanan M, Lee HS, Lee H, Chang MW, Ching CB, Ahn J, Lee DY

Biotechnology and Bioengineering 113: 1993-2004 (2016)


2015

SynLinker: an integrated system for designing linkers and synthetic fusion proteins

Liu CC, Chin JX, Lee DY

Bioinformatics 22:3700-3702 (2015)

Synthetic fusion protein design and applications

Yu K, Liu CC, Kim BG, Lee DY

Biotechnology Advances 33:155-164 (2015)

Effect of linker flexibility and length on the functionality of a cytotoxic engineered antibody fragment

Klement M, Liu CC, Loo BLW, Choo ABH, Ow DSW, Lee DY

Journal of Biotechnology 199: 90-97 (2015)

In silico model-driven cofactor engineering strategies for improving the overall NADP(H) bioavailability in microbial cell factories

Lakshmanan M, Yu K, Koduru L, Lee DY

Journal of Industrial Microbiology and Biotechnology 42: 1401-1414 (2015)

Epoxide hydrolase-lasalocid A structure provides mechanistic insight into polyether natural product biosynthesis

Wong FT, Jotta K, Chen X, Fang M, Watanabe K, Kim CY

Journal of the American Chemical Society 137: 86-89 (2015)

Combinatorial metabolic engineering of Saccharomyces cerevisiae for terminal alkene production

Chen BB, Lee DY, Chang MW

Metabolic Engineering 31:53-61 (2015)

Bacterial XylRs and synthetic promoters function as genetically encoded xylose biosensors in Saccharomyces cerevisiae

Teo WS, Chang MW

Biotechnology Journal 10:315-322 (2015)

Matrix-immobilized yeast for large-scale production of recombinant human lactoferrin

Ho CL, Hwang IY, Loh K, Chang MW

Med Chem Comm 6:486-491 (2015)

Engineering transcription factors to improve against alkane biofuels in Saccharomyces cerevisiae

Ling H, Pratomo NK, Teo WS, Liu R, Leong SSJ, Chang MW

Biotechnology for Biofuels 8:231-242 (2015)

Metabolic engineering of Saccharomyces cerevisiae for production of fatty acid short- and branched-chain alkyl esters biodiesel

Teo WS, Yu A, Chang MW

Biotechnology for Biofuels 8:177-185 (2015)

Synthetic polyketide enzymology: platform for biosynthesis of antimicrobial polyketides

Go M, Wongsantichon J, Cheung, VWN, Chow JY, Robinson RC, Yew WS

ACS Catalysis 5:4033-4042 (2015)

Engineered strains enhance gold biorecovery from electronic scrap

Natarajan G, Tay SB, Yew WS, Ting YP

Minerals Engineering 75:32-37 (2015)

Engineered Saccharomyces cerevisiae to produce odd chain-length fatty alcohols

Jin Z, Wong A, Foo JL, Ng Joey, Cao YX, Chang MW, Yuan YJ

Biotechnology and Bioengineering 113:842-851 (2015)


2014

Production of fatty acid-derived valuable chemicals in synthetic microbes

Yu AQ, Pratomo Juwono NK, Leong SSJ, Chang MW

Frontiers in Bioengineering and Biotechnology 2:78-89 (2014)

Microbial tolerance engineering toward biochemical production: from lignocellulose to products

Ling H, Teo W, Chen B, Leong SSJ, Chang MW

Current Opinion in Biotechnology 29:99-106 (2014)

Site specific immobilization of a potent antimicrobial peptide onto silicone catheters: evaluation against urinary tract infection pathogens

Mishra B, Basu A, Chua RRY, Saravanan R, Tambyah PA, Ho B, Chang MW, Leong SSJ

Journal of Materials Chemistry 2:1706-1716 (2014)

Therapeutic microbes for infectious disease

Wong CK, Tan MH, Rasouliha B, Hwang IY, Ling H, Poh CL and Chang MW

Methods in Molecular Biology 1151:117-133 (2014)

Identification of polyketide inhibitors targeting 3-dehydroquinate dehydratase in the shikimate pathway of Enterococcus faelis

Cheung VWN, Xue B, Valladares MH, Go M, Tung A, Aguda AH, Robinson RC, Yew WS

PLoS ONE 9:e103598 (2014)

Glycine decarboxylase is an unusual amino acid decarboxylase involved in tumorigenesis

Go M, Zhang WC, Lim B, Yew WS

Biochemistry 53: 947-956 (2014)

Disruption of Biofilm Formation by the Human Pathogen Acinetobacter baumannii using engineered quorum-quenching Lactonases

Chow JY, Yang Y, Tay SB, Chua KL, Yew WS

Antimicrobial Agents and Chemotherapy 58: 1802-1805 (2014)


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