Research areas and topics

My research interests are metabolic pathway engineering and the development of recombinant DNA tools to modify and introduce existing or entirely new metabolic pathways and regulatory systems within cells to improve their capacity for overproduction of desired molecules (Biofuels, Bioplastics,  Chemicals, Cosmetics, Drugs).   

Specific research areas include:

    ■ Gene discovery                                                                                                          ■ Protein engineering

    ■ Development of gene expression systems                                               ■ Metabolic pathway regulation

    ■ Metabolic pathway optimization using functional genomics       ■ Synthetic biology

Specific research topics

Research 1: Design and development of synthetic bacteria utilizing cellulosic substrates

1. Engineering E. coli and P. putida capable of co-utilizing glucose and xylose

2. Engineering C. cauae and M. extorquens capable of co-utilizing of glucose and xylose

3. Engineering bactria for levulinic acid refinery

Research 2: Metabolic engineering of central metabolic pathways 

1. Cyclic operation of the pentose phosphate pathway (PPP) 

2. Activation of ED and inactivation of EMP 

3. Control of NADH/NADPH ratio 

Research 3: Metabolic engineering of target biosynthesis pathways 

1.  Production of biopolymer (PHA) and monomers (3HP, 3HV & 4HV)

2. Production of fatty acids & jet fuel 

3. Production of 2,3-BDO, etc.

Research 4: Development of next-generation synthetic biology tools 

1. Development of genome editing tools 

2. Development of biosensors for target compounds 

1. Design and development of synthetic cellulolytic bacteria

An efficient cellulolytic organism for commercial biofuel production should be able to completely hydrolyze cellulosic biomass and ferment all sugars of the hydrolysate  simultaneously. Despite the diversity of cellulolytic organisms and their efficient innate potential, their implications in biofuel research are limited owing to the poor knowledge of their overall metabolic network and the lack of genetic and molecular biology tools available to manipulate them to be an efficient solventogen.Therefore, there is the need to engineer model organisms like Escherichi coli and Pseudomonas putida to incur cellulolytic ability.

     - Engineering cellobiose metabolic pathway in E. coli and P. putida

     - Expression of cellulases in E. coli and P. putida

  2. Metabolic engineering of central metabolic pathways

  E. coli and P. putida have been used routinely in molecular biology as both a tool and a model organism because it can be genetically manipulated very easily. However, both species are not evolved to an ideal host strain to produce chemicals from lignocellulosic biomass. This means that their central metabolic pathways should be engineered to produce large quantities of target products.  Biosynthetic reactions require NADH or NADPH as reducing power; NADPH for FAs/DCAs/3-HP and NADH for lactate/2,3BDO. Controlling NADH/NADPH ratio, as well as regeneration of NADH and NADPH, is also important for maximal production of target compounds. 

 3. Metabolic engineering of target biosynthesis pathways 

This research aims to develop mutant Escherichia coli strain which has enhanced ability to produce 3-HP in terms of titer and productivity. 3-Hydroxypropionic acid (3-HP) is a platform chemical of which bi-functionality allows it to be further transformed into a variety of high value compounds such as acrylic acid, acrylamide, propiolactone and acrylonitrile. Three strategies are considered to achieve the goal: increase in accumulation of reducing power and precursor, improve in key enzyme activity. First, combination of genome engineering of  the central carbon metabolism and evolutionary adaptation leads to mutant with highly accumulated NADPH, which is required for converting malonyl-CoA to 3-HP. Second, the side pathway deletion and down regulation are expected to increase yield. Finally, by isolating mutant malonyl-CoA, the key enzyme, titer and productivity might be increased.

 4. Development of next generation synthetic biology tools

Rapid advances in recombinant DNA technology, functional genomics, analytical technologies, the design of artificial biological systems and the understanding of their natural counterparts, known as synthetic biology, will extend the application of biosystems engineering such as metabolic engineering, systems biology.