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.<br />
 
'''DEBS1''' is acylated by a diketide at module 2<ref>PMID:8952473</ref>.<br />
'''DEBS3''' carries out the final two cycles in the synthesis of 6-dEB<ref>PMID:9538011</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>
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