6-deoxyerythronolide B synthase (DEBS): Difference between revisions

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[[Image:DEBS.png|left|500px|thumb|6-deoxyerythronolide B synthase (DEBS)]]
[[Image:DEBS.png|left|500px|thumb|6-deoxyerythronolide B synthase (DEBS)]]
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The 6-deoxyerythronolide B synthase (DEBS), which catalyzes the formation of 6-dEB, consists of three large subunits, DEBS1, DEBS2 and DEBS3, each containing two modules and above 300 kD in size. There are 2 domains in the N-terminal loading module, responsible for priming the synthase with a proprionate starter unit, and 26 domains in the six extender modules, Each extender module contains at least three essential domains: a ketosynthase (KS), an acyl transferase (AT) and an acyl carrier protein (ACP). In detail, the AT domain selects the appropriate carbon extender unit and transfers the units from acyl-CoA onto the phosphopantetheine arm of ACP. The KSdomain accepts the polyketide chain from the previous module and catalyzes chain elongation reaction by adding an ACP-bound extender unit through decarboxylative condensation.
The '''6-deoxyerythronolide B synthase''' (DEBS), which catalyzes the formation of 6-dEB, consists of three large subunits, DEBS1, DEBS2 and DEBS3, each containing two modules and above 300 kD in size. There are 2 domains in the N-terminal loading module, responsible for priming the synthase with a proprionate starter unit, and 26 domains in the six extender modules, Each extender module contains at least three essential domains: a ketosynthase (KS), an acyl transferase (AT) and an acyl carrier protein (ACP). In detail, the AT domain selects the appropriate carbon extender unit and transfers the units from acyl-CoA onto the phosphopantetheine arm of ACP. The KSdomain accepts the polyketide chain from the previous module and catalyzes chain elongation reaction by adding an ACP-bound extender unit through decarboxylative condensation.


After the extender unit is added, it can be further processed by optional tailoring domains, including ketoreductases (KRs), dehydratases (DHs), and enoyl reductases (ERs), to yield a hydroxyl, enoyl, or methylene group at the beta-position. Finally, the thioesterase (TE) domain that located at the C-terminus of DEBS module 6 promotes  the macrocyclization event which releases the final product, 6-dEB. <ref>PMID:17328673</ref>
After the extender unit is added, it can be further processed by optional tailoring domains, including ketoreductases (KRs), dehydratases (DHs), and enoyl reductases (ERs), to yield a hydroxyl, enoyl, or methylene group at the beta-position. Finally, the thioesterase (TE) domain that located at the C-terminus of DEBS module 6 promotes  the macrocyclization event which releases the final product, 6-dEB. <ref>PMID:17328673</ref>

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Tsung-Yi Lin, Jon Amoroso, David Canner, Lawrence Sheringham Borketey, Jaime Prilusky, Michal Harel, Alexander Berchansky, Joel L. Sussman