Detailed Task C1_Joint 1_ Marine Microorganisms Genomic Information Analysis and Utilization of the Foundation (KAP220273)
Establishment of genome-based useful marine microorganism strain discovery system Detoxification of whole genomes of 64 marine microorganisms Discover 400 types of useful genes (biosynthesis/modified genes, etc. of bioactive substances) from the detoxed whole genome Development of an efficient expression activation system and heterologous cell factory for large biosynthetic gene groups derived from marine microorganisms Discovering 28 kinds of new physiologically active substances derived from marine microorganism genomes and strains and identifying their structures Discovery of new high-functioning physiologically active substances (more than types) through activity evaluation and identification of biosynthetic mechanisms Establishment of source technology for structural modification of synthetic biological and physiologically active substances and deriving leading substances through activity improvement/optimization/mass production (more than one type) Discover more than proteins that can be used industrially based on the genome of marine microorganisms and identify their functions Isolation and securing of microorganisms for genome decoding Useful microorganisms: selection of candidate species based on bioactivity and genome scanning Pathogenic microorganisms: Isolation from dead fish and distribution of representative strains to related institutions Standard microorganisms: Use of strains previously secured by researchers, strain banks, and strains recommended by the Species Selection Committee Construction of marine microorganism DNA library and selection of useful microorganisms Construction of DNA library of 2,000 species of marine bacteria including first-stage construction DNA library PCR primer for DNA library screening (18 structure parent nucleus) Establishment and operation of new bioactive substance discovery system based on marine microorganism genome using PCR primer Production of useful physiologically active substances Used for selection of marine microorganism strains Detoxification of whole genomes of 64 marine microorganisms (useful/pathogenic/standard) Detoxification of the whole genome of 40 useful microorganisms: microorganisms producing physiologically active substances such as antibiotics and anticancer substances Detoxification of the whole genome of hospital microorganisms: fish disease pathogens, microorganisms, etc. Whole genome detoxification of 20 standard microorganisms: marine dominance, ecological function, classification standard microorganism reference genome Discovering useful genes from the detoxified whole genome Biosynthesis of bioactive substances/modified genes, etc. Discovering functional genes such as polyketide synthase and non-ribosomal peptide synthase Utilization of various platforms: discovering BGC Analysis of the characteristics of excavated genes using multi-omics approaches, etc. Development of an efficient expression activation system and heterologous cell factory for large biosynthetic gene groups derived from marine microorganisms Establishment of genome editing system capable of controlling gene manipulation and promoter substitution that induces the expression of biosynthetic gene groups of bioactive substances in marine microorganisms Development of heterogeneous host cell factory capable of efficiently expressing large biosynthetic gene clusters when genetic manipulation of marine microorganisms is impossible Discovering new bioactive substances and identifying their structures Selection, expression activation, and culture of production strains of material containing important parental nuclei by DNA library search Chemical analysis of the culture solution of marine microorganism strains (using LC/MS) Mass culture of new bioactive material production strains (>20 L) Separation and purification of new physiologically active substances by chromatography (28 types) Identification of material structure by spectroscopic analysis (28 types) Research on the bioactivity and biosynthesis of new substances In vitro search for antimicrobial efficacy such as antibacterial and antifungal In vitro search for anticancer-related efficacy Further search for other bioactivity Excavation of types of high-functioning physiologically active substances and identification of biosynthetic mechanisms Active improvement/optimization/mass production through structural modification of useful physiologically active substances, and discovery of leading substances through identification of physiological activities Selected as one high-potency bioactive substance Identification of in vitro level physiological activity and toxicity of one useful physiologically active substance Mass production by heterogeneous host biofactory mass production of material (>100 mg) through optimization of the culture process of natural strains and securing the amount of material for in vivo physiological activity Discover more than proteins used in the marine microbial genome-based industry and identify their functions Elastase inhibitory protein using Altibacter jejuensis genome information Celeribacter marinus phage/bacterial genome-conjugated acetylase enzyme Novel DNA polymerase using Puniceispirillum marinum bacteria-phage system, etc. Discovery of more than final cases including marine genomes and useful protein genes related to new useful microorganisms and pathogenic bacteria scheduled for annual analysis Technical Aspects. Despite the academic excellence, the biggest reason for the difficulty in developing new drugs from marine natural products is the difficulty in securing various bioactive substances and the inefficiency of this process. The greatest technical achievement of this study is the development of method to efficiently and economically connect the basic technology and the developed technology by overcoming the large gap between the research on bioactive marine natural products and the research on new drug development. In particular, it is easy to access biologically such as culture and genetic recombination, and the structural diversity and novelty of compounds and the frequency of discovery of physiological activities are high, so the potential for new drug candidates is high. Derivative research is also active in marine microorganisms. This study, which is of an intermediary nature to solve the obstacles of industrial R&D of. Promote the overall and comprehensive improvement of the R&D level of marine natural products and improve the core biological and chemical unit technologies close to the world level. Propose new strategy in the field of bioactive natural product research technology using marine microorganism genome information and secure future source technology. Promote transfer and expansion of bioactive substances targets for new drug development from terrestrial organisms to marine microorganisms. Ripple effect on adjacent technologies: Since marine microorganism genome utilization research is multi-disciplinary research, research tools (genomic analysis, strains, extracts and natural products) and essential information (genomic information BGC information, structure and physical properties of compounds, and physiological activity) will contribute to the development of research in the relevant field, and through this, mutual exchange between adjacent research fields and convergence of academic and technological development are expected.. Cultivation of professional research manpower with core technology for marine microbial genome-based drug development: significant part of the backwardness of marine microbial genome utilization and marine natural product drug development in Korea is due to the absolute lack of advanced manpower in the relevant field. This research project will produce large number of professional manpower, which will greatly contribute to the enhancement of research capabilities in the field of domestic genome-based marine natural products, pharmaceuticals, and marine biotechnology.  Economic and industrial aspects. From an industrial point of view, the most important application of marine microbial genomes is to provide materials for new drugs. BGC discovery and creation of new pharmacophores induce economic effects of high added value along with the development of new drug-related industries following the development of new drug lead materials. In addition, when it is developed as research reagent for biochemical and pharmacological research, it produces considerable economic effects. This is achieved by commercialization of discovered drugs and industrialization of original technology.. Direct economic effect: If successful in the development of new natural products, economic value such as royalties are created.. Inducing the R&D of new natural products in the industry: We will provide motivation and technology to induce the domestic marine natural product-related industry, which is focusing on low value-added products such as cosmetics and health supplements, to develop new natural products.  Social aspect. If the successful implementation of this study enters the process of using marine microbial genome information and developing new drugs, it will bring about shift in social interest and awareness about the enormous genomic resources of marine microorganisms and marine-derived natural products in relation to the quality of life. It will make great contribution to society in terms of entry of the next academic generation, establishment and expansion of research and support institutions, and job creation.