2013 Fiscal Year Final Research Report
Structure-activity relationship of lariatin
| Project/Area Number |
23510282
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Chemical biology
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2013
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| Keywords | 抗結核活性 / 構造活性相関 |
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| Research Abstract |
Lariatins A and B discovered as an anti-mycobacterial peptides are ribosomally synthesized by Gram positive Rhodococcus jostii. The compounds are unique cyclic peptides, the rigid lasso structure. Production of lariatins in R. jostii is dependent upon a five-gene cluster, larA to larE. We established a simple system of amino acid substitutions of lariatin by R. jostii delta larA, Using this system, mutational scanning of lariatin was carried out. The results showed that three aa residues (G1, R7 and E8) in the circle and three aa residues (W9, V10 and G11) in the threaded segment of the tail are important for lariatin production, and that two aa residues (Y6 and R7) in the circle and four aa residues (7R7, V10, N14 and K17) in the threaded segment of the tail are important for anti-mycobacterial activity. Propeptin biosynthesis gene cluster was identified on the genome of Microbispora rosae. The gene cluster containing the genes corresponding to lar A , B, C and D, but not lar E.
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