Trường Đại Học Mở Hà Nội

Mining novel compounds and development of functional probiotics from microbial library

Joo-Won Suh, Ph.D. Director¹ & CEO²

¹Myongji Bioefficacy Research Center, Myongji University, Yongin, Gyeonggi-do, Republic of Korea

²Microbiohealthcare Co. Ltd. Yongin, Gyeonggi-do, Republic of Korea

E-mail: jwsuh@mju.ac.kr

ECUM, an Extract Collection of Useful Microorganisms, encompasses over 20,000 strain of actinomycetes, and food microbial strains. These strains were isolated from ecologically distinctive soil, food and human resource, aiming to isolate unique and uncharacterized metabolites. Through one of this effort, Ecumicin, a novel cyclic peptide compound with strong anti-tuberculosis activity, was isolated from Nonomuraea sp MJM5123 in ECUM library. Rufomycin, another cyclic peptide with strong anti-tuberculosis activity, was also discovered from Streptomyces sp. MJM3502 in this library. The MIC₉₀ of ecumicin and rufomycin was analyzed to be 0.16 and 0.019 μM against drug susceptible M. tuberculosis, outperforming other compounds targeting M. tuberculosis ClpC1. Notably, Ecumicin and rufomycin showed excellent activity against both multidrug-resistant M. tuberculosis (MDR-TB) and extensively drug-resistant M. tuberculosis (XDR-TB), while exhibiting no activity against other microorganisms like Escherichia coli, Candida albicans and Staphylococcus aureus. Finally, we discovered that ecumicin and rufomycin bind to ClpC1 at different binding sites and different stochastic ratio compared to other compounds that also target ClpC1, suggesting the potential for ecumicin and rufomycin to be used in combination therapy with each other or other drugs. These finding suggest that ecumicin and rufomycin can be developed as novel anti-tuberculosis drugs for treating MDR-TB and XDR-TB, providing an alternative to existing treatment. Due to the novel chemical structure and promising activity of ecumicin, international patents were already granted in several leading countries including USA. We also have selected functional probiotics for oral health, anti-obesity, liver health, kidney health, cholesterol lowering etc. Those strains are waiting for commercial development in Korea as well as in Vietnam. We are currently seeking partnerships with companies, institutes, and business collaboration for further development.

Natural approach of strain improvement

Sailesh Malla, PhD, Principal Research Scientist

Strain Improvement Department, Microbe Culture and Research, R&D, Novonesis, Denmark

Abstract

Unicellular microorganisms (bacteria) actively participate in various biological processes. Upon proper strain improvement, either by natural strain improvement methods or metabolic engineering approaches, and/or process optimizations, these microbes can acquire incredible potential to benefit the world for sustainable development in food, agriculture, pharma-industries, therapeutics, etc. Over the past few decades, researchers have discovered and developed various natural strain improvement strategies, molecular biology tools and techniques to adapt and improve bacteria for various biotechnological applications. Furthermore, the new developments in various -omics technologies (such as metabolomics, proteomics, genomics, metagenomics, etc.) including next generation sequencing technology and analytical instrumentation have significantly sophisticated the understanding of complex biological processes in the molecular and genetic level.

We apply natural strain improvement approaches such as Adaptive Laboratory Evolution (ALE), direct selection strategies, mutagenesis and high-throughput selection for improving our industrial strains which are subsequently used to develop food cultures for application in various food-based products. In addition, I will present some cases of strain improvement, that are used to develop plant health care products.