1995 Fiscal Year Final Research Report Summary
SEARCH OF NOVEL BIOACTIVE NATURAL PRODUCTS BASED ON MOLECULAR EVOLUTION OF SYNTHETASES
| Project/Area Number |
06660134
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Bioproduction chemistry/Bioorganic chemistry
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
NISHIOKA Takaaki KYOTO UNIVERSITY,INSTITUTE FOR CHEMICAL RESEARCH,ASSOCIATE PROFESSOR, 化学研究所, 助教授 (80026559)
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| Project Period (FY) |
1994 – 1995
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| Keywords | NATURAL PRODUCTS / METABOLISM / METABOLIC PATHWAYS / ENZYME / DATABASE / MOLECULAR EVOLUTION / LEAD STRUCTURE / DRUG DESIGN |
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| Research Abstract |
MOST COMMON SOURCES OF LEAD STRUCTURES OF DRUGS FOR MEDICINAL USES ARE BIOACTIVE NATURAL PRODUCTS PRODUCED BY MICROORGANISMS AND PLANTS.THE PROBABILITY OF FINDING NOVEL STRUCTURE IS VERY SCARCE BECAUSE THE SEARCH OF BIOACTIVE PRODUCTS DEPENDS ON RANDOM SCREENING OF LIVING ORGANISMS.NO PRACTICAL RATIONAL DRUG DESIGN IS APPLICABLE TO LEAD STRUCTURE DISCOVERY.THE PRESENT RESEARCH PROJECT HAVE DEVELOPED A RATIONAL METHOD OF FINDING NATURAL PRODUCTS : THAT IS,IT PREDICTS UNKNOWN NATURAL PRODUCTS BY CONSTRUCTING ALL POSSIBLE METABOLIC PATHWAYS BASED ON GENOME DNA SEQUENCES AND MOLECULAR EVOLUTION OF SYNTHETIC ENZYMES.WITH THE PROGRESS OF GENOME PROJECTS.THE WHOLE GENES BECOME IDENTIFIED FOR AN ORGANISM.IN OTHER WORDS,UNKNOWN METABOLIC PATHWAYS TO NATURAL PRODUCTS COULD BE PREDICTED FROM A SET OF ENZYMES PREDICTED FROM THEIR GENES.THE INVESTIGATOR FIRST COMPILED 1987 KNOWN METABOLITES AND 96 MAIN METABOLIC PATHWAYS.FOR A GIVEN COMPOUND.ALL OF THE ENZYMES PRODUCING IT AS A METABOLITE ARE LISTED BASED ON THE LIGAND CHEMICAL DATABASE WHICH HE PREVIOUSLY CONSTRUCTED DATABASE FOR ENZYMATIC REACTIONS.FOR EXAMPLE,L-GLUTAMATE IS A PRODUCT OR SUBSTRATE OF 87 DIFFERENT ENZYMES.BY CONNECTING THE METABOLITES WITH THESE ENZYMES, POSSIBLE PATHWAYS ARE GENERATED.THE PATHWAYS GENERATED,HOWEVER,ARE TOO COMPLICATED.ACTUAL LIVING ORGANISMS USE ONLY A LIMITED NUMBER OF PATHWAYS.UNKNOWN METABOLIC PATHWAYS ARE PRESENTED AS THE DIFFERENCE OF THOSE CONSTRUCTED AND THOSE KNOWN.
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