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Chain Elongation and Cyclization in Type III PKS DpgA
Author(s) -
Wu HaiChen,
Li YiSan,
Liu YuChen,
Lyu SyueYi,
Wu ChangJer,
Li TsungLin
Publication year - 2012
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201200051
Subject(s) - polyketide , chemistry , stereochemistry , molecule , polyketide synthase , elongation , biosynthesis , biochemistry , organic chemistry , enzyme , materials science , metallurgy , ultimate tensile strength
Chain elongation and cyclization of precursors of dihydroxyphenylacetyl‐CoA (DPA‐CoA) catalyzed by the bacterial type III polyketide synthase DpgA were studied. Two labile intermediates, di‐ and tri‐ketidyl‐CoA (DK‐ and TK‐CoA), were proposed and chemically synthesized. In the presence of DpgABD, each of these with [ 13 C 3 ]malonyl‐CoA (MA‐CoA) was able to form partially 13 C‐enriched DPA‐CoA. By NMR and MS analysis, the distribution of 13 C atoms in the partially 13 C‐enriched DPA‐CoA shed light on how the polyketide chain elongates and cyclizes in the DpgA‐catalyzed reaction. Polyketone intermediates elongate in a manner different from that which had been believed: two molecules of DK‐CoA, or one DK‐CoA plus one acetoacetyl‐CoA (AA‐CoA), but not two molecules of AA‐CoA can form one molecule of DPA‐CoA. As a result, polyketidyl‐CoA serves as both the starter and extender, whereas polyketone‐CoA without the terminal carboxyl group can only act as an extender. The terminal carboxyl group is crucial for the cyclization that likely takes place on CoA.