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Biosynthetic Multitasking Facilitates Thalassospiramide Structural Diversity in Marine Bacteria.
- Source :
-
Journal of the American Chemical Society . 1/23/2013, Vol. 135 Issue 3, p1155-1162. 8p. - Publication Year :
- 2013
-
Abstract
- Thalassospiramides A and B are immunosuppressant cyclic lipopeptides first reported from the marine α-proteobacterium Thalassospira sp. CNJ-328. We describe here the discovery and characterization of an extended family of 14 new analogues from four Tistrella and Thalassospira isolates. These potent calpain 1 protease inhibitors belong to six structure classes in which the length and composition of the acylpeptide side chain varies extensively. Genomic sequence analysis of the thalassospiramide-producing microbes revealed related, genus-specific biosynthetic loci encoding hybrid nonribosomal peptide synthetase/polyketide synthases consistent with thalassospiramide assembly. The bioinformatics analysis of the gene clusters suggests that structural diversity, which ranges from the 803.4 Da thalassospiramide C to the 1291.7 Da thalassospiramide F, results from a complex sequence of reactions involving amino acid substrate channeling and enzymatic multimodule skipping and iteration. Preliminary biochemical analysis of the N- terminal nonribosomal peptide synthetase module from the Thalassospira TtcA megasynthase supports a biosynthetic model in which in cis amino acid activation competes with in trans activation to increase the range of amino acid substrates incorporated at the N terminus. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00027863
- Volume :
- 135
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Journal of the American Chemical Society
- Publication Type :
- Academic Journal
- Accession number :
- 85344352
- Full Text :
- https://doi.org/10.1021/ja3119674