Active Site Comparisons and Catalytic Mechanisms of the Hot Dog Superfamily

In vitro kinetic study of the squalestatin tetraketide synthase dehydratase reveals the stereochemical course of a fungal highly reducing polyketide synthase

“…17 In particular the DH domain from CurF, 18 a modular type I PKS, formed an appropriate template for the assembly of a model by the SwissModel threading server. 19 Comparison of the results showed that the backbone atoms of the SQTKS DH model and CurF-DH had only 1.4 Å root mean square deviation (RMSD).…”

Polyene macrolide biosynthesis in streptomycetes and related bacteria: recent advances from genome sequencing and experimental studies

“…C1 and C2 KRs do not reduce the -ketone but give (2R)-and (2S)-2-methyl-3-ketoacyl products, respectively. [The reasons for using both relative (L and D) and absolute (R and S) indictators when describing polyketide stereochemistry have been explained by Labonte and Townsend (2013).] Crystal structures have now been determined for seven PKS KR domains, including the A1 KR2 and A2 KR11 domains of the amphotericin PKS (Bonnett et al, 2013).…”

“…Some of these result from trans-cis isomerisation (Perlova et al, 2006;Vergnolle et al, 2011) or late modification (Palaniappan et al, 2008), others from dehydration of 3L-3-hydroxyacyl chains by the PKS. In these last cases, DH domains are paired with A-type KRs (Alhamadsheh et al, 2007;Labonte and Townsend, 2013).…”

An Unusual Dehydratase Acting on Glycerate and a Ketoreducatse Stereoselectively Reducing α‐Ketone in Polyketide Starter Unit Biosynthesis

“…Asp is on a helix of the C-terminal hotdog. [17] In the present work, it was confirmed that the two DH*-like proetins (Fr9C-DH* and Orf19-DH*) function as DHs acting on the glyceryl-S-ACP substrate; however, further bioinformatic analysis of these DH*-like enzymes suggested that these proteins belong to a family of MaoC-like dehydratases (pfam 01575, Supporting Information, Figure S6), which usually act as (R)-specific enoyl-CoA hydratase and have a conserved catalytic DxxxxH motif. [18] The Asp residue activates a water to attack the C3 carbon of the substrate, and the His residue donates a proton to the C2 carbon.…”