InChI=1S/C38H66N7O19P3S/c1-4-5-6-7-8-9-10-11-12-13-14-15-16-25(36(50)51)37(52)68-20-19-40-27(46)17-18-41-34(49)31(48)38(2,3)22-61-67(58,59)64-66(56,57)60-21-26-30(63-65(53,54)55)29(47)35(62-26)45-24-44-28-32(39)42-23-43-33(28)45/h23-26,29-31,35,47-48H,4-22H2,1-3H3,(H,40,46)(H,41,49)(H,50,51)(H,56,57)(H,58,59)(H2,39,42,43)(H2,53,54,55)/p-5/t25?,26-,29-,30-,31+,35-/m1/s1 |
XUKMCVIPGKHZGR-QGGHQSAPSA-I |
CCCCCCCCCCCCCCC(C([O-])=O)C(=O)SCCNC(=O)CCNC(=O)[C@H](O)C(C)(C)COP([O-])(=O)OP([O-])(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1OP([O-])([O-])=O)n1cnc2c(N)ncnc12 |
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2-carboxyhexadecanoyl-CoA
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UniProt
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2-carboxyhexadecanoyl-CoA(5−)
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ChEBI
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2-carboxyhexadecanoyl-coenzyme A(5−)
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ChEBI
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2-carboxypalmitoyl-coenzyme A(5−)
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ChEBI
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Gavalda S, Léger M, van der Rest B, Stella A, Bardou F, Montrozier H, Chalut C, Burlet-Schiltz O, Marrakchi H, Daffé M, Quémard A (2009) The Pks13/FadD32 crosstalk for the biosynthesis of mycolic acids in Mycobacterium tuberculosis. The Journal of biological chemistry 284, 19255-19264 (Source: SUBMITTER) [PubMed:19436070] [show Abstract] The last steps of the biosynthesis of mycolic acids, essential and specific lipids of Mycobacterium tuberculosis and related bacteria, are catalyzed by proteins encoded by the fadD32-pks13-accD4 cluster. Here, we produced and purified an active form of the Pks13 polyketide synthase, with a phosphopantetheinyl (P-pant) arm at both positions Ser-55 and Ser-1266 of its two acyl carrier protein (ACP) domains. Combination of liquid chromatography-tandem mass spectrometry of protein tryptic digests and radiolabeling experiments showed that, in vitro, the enzyme specifically loads long-chain 2-carboxyacyl-CoA substrates onto the P-pant arm of its C-terminal ACP domain via the acyltransferase domain. The acyl-AMPs produced by the FadD32 enzyme are specifically transferred onto the ketosynthase domain after binding to the P-pant moiety of the N-terminal ACP domain of Pks13 (N-ACP(Pks13)). Unexpectedly, however, the latter step requires the presence of active FadD32. Thus, the couple FadD32-(N-ACP(Pks13)) composes the initiation module of the mycolic condensation system. Pks13 ultimately condenses the two loaded fatty acyl chains to produce alpha-alkyl beta-ketoacids, the precursors of mycolic acids. The developed in vitro assay will constitute a strategic tool for antimycobacterial drug screening. |
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