Microbial cell factories offer extensive opportunities for the industrial production of complex biomolecules for cost effective biological synthesis. Furthermore, microbial fermentation often reduces the need for energy-intensive reaction conditions, toxic organic solvents, heavy metal catalysts, and strong acids/bases, which are widely utilized in chemical synthesis routes. Among the microbial cell factories design the Gram-negative bacterium Escherichia coli has become one of the most promising hosts, with a highly tractable genetic system and favorable fermentation conditions for production purposes.
The flavonoid biosynthetic pathway has been almost completely elucidated. Many of the structural genes have been cloned from several organisms (especially from plant, fungi and bacteria) for efficient production of flavonoids. In addition, we have incorporated the regiospecific post-tailoring enzymes to produce flavonoid derivatives in E.coli.
Similarly, alkaloids, a diverse group of nitrogen-containing natural products, are produced by a large variety of organisms including bacteria, fungi, insects, plants and animals. Since alkaloids are toxic, they are usually produced in small quantities by their native producer organisms. By heterologous pathway expression from cyanobacteria into E. coli, we have produced Scytonemin precursor, a natural sunscreen alkaloid compound with cytotoxic activity.
Hence, we have engineered the E.coli strains for sustainable production of the bioactive natural products such as flavonoids and alkaloids.
Sailesh Malla (PhD) is currently a researcher at Novo Nordisk Foundation Center for Biosustainability (NNF-CFB) at Technical University of Denmark. He is a microbial biotechnologist and mainly conducting his research on microbial engineering for various industrial and pharmaceutical aspects.
Dr. Malla received his PhD in Biochemistry from life science and pharmaceutical engineering department at Sun Moon University, South Korea in 2009. From 2009 to 2012, as a postdoctoral researcher in Seoul National University, South Korea, he mainly worked for microbial production of plant natural products. Then he joined NNF-CFB in 2012. He has been actively conducting his research in the areas such as metagenomics, genome engineering, metabolic engineering, adaptive evolution, biosynthetic pathway discoveries, etc. Dr. Malla has published more than 15 well cited international peer-reviewed journals. He has been serving as an editorial broad member in EC Microbiology Journal.
Title of the talk: Metabolic engineering and microbial physiology for simultaneous production of multiple fuels and chemicals using a single microorganism
Microorganisms have evolved to optimize their growth, rather than the formation of metabolite(s) useful to human. Microbial growth occurs with or through generation of multiple metabolites, but metabolic engineering usually focuses on the production of a ‘single’ compound by re-designing metabolic pathways. This often seriously interferes with cellular metabolisms, hurts cell growth and viability, and makes the microorganism to function inefficiently as microbial cell factory. Production of properly-selected, multiple metabolites, instead of a single metabolite, can offer flexible balancing of the in vivo metabolic flux and easier maintenance of cellular homeostasis including redox state. To demonstrate the potential of the co-production strategy, we have studied Klebsiella pneumoniae for co-production of 3-hydroxypropionic acid (3-HP) and 1,3-propanediol (1,3-PDO) or 1,3-PDO and 2,3-butanediol (2,3-BDO) from glycerol, and Escherichia coli for co-production of H2 and ethanol or 3-HP from glucose. Co-production of 3-HP and 1,3-PDO made the generation and consumption of NAD(H) well-balanced, reduced the accumulation of the toxic intermediate, 3-hydroxypropionaldehyde, and resulted in high glycerol-to-products yield (>0.8) at high titer (>70 g/L). Co-production of 1,3-PDO and 2,3-BDO by K. pneumoniae alleviated metabolic traffic at the pyruvate node, reduced acetate accumulation, and enabled the maintenance of redox balance. Co-production of H2 and ethanol from glucose required the re-direction of carbon flux to the Pentose Phosphate (PP) pathway from the Embden-Myerhoff-Parnas (EMP) pathway. Increase in NAD(P)H supply enhanced ethanol production, and H2 and ethanol could be obtained with the theoretical maximum yields and negligible acetate. This lecture also discusses the challenges of the co-production strategy.
Prof. Sunghoon Park received Ph.D. degree in Chemical Engineering from University of California, Davis in 1988. He worked for CKD Pharmaceutical Co, Seoul, Korea in 1982-84, and Lawrence Livermore National Laboratory, CA, USA in1988-91. Since 1991, he is Professor at the School of Chemical and Biomolecular Engineering, Pusan National University (PNU), Korea. Dr. Park is former Editor-in-Chief of Biotechnology and Bioprocess Engineering (BBE) and currently, a Senior Editor of Journal of Industrial Microbiology and Biotechnology (JIMB). Major research interest lies in metabolic engineering and synthetic biotechnology for microbial production of biofuels and biochemicals from renewable resources. Dr. Park has published over 170 papers in peer-reviewed journals and holds >30 patents.