Phylogenetic Analysis And Molecular Modeling Study Of Antibiotic Thioesterase

Polyketides antibiotics constitute a large and structurally diverse class of natural products that exhibit many important biological activities. During their biosynthesis and release, there exits a kind of enzyme called thioesterase which play an important role not only in the releasing of final product, but also in deblocking the misprimed substrates during the chain elongation. This paper reconstructed the molecular phylogenetic trees of TEs from NCBI database with neighbor-joining and maximum-likelihood methods of phylogenetic inference, which show that the Tes in the streptomyces fall into three categories. Of the three there are a kind of acyl-CoA TEâ…¡in just five kinds of streptomyces.After sequences and structure analysis of these enzymes, it concludes that they belong to the TesB family, and their functions may be deblocking the misprimed acyl-CoA substrates. Based on the structure diversity of DEBS TE and PICS TE under different pH, this paper use using FlexX in SYBYL6.92 software package to find out the pH effect on the activity of the enzymes. The docking results reveal that, the activity of the PICS TE enhances according to the ascending pH from 7.6 to 8.4, while the DEBS TE lose its activity totally under the pH8.5. The results reveals that TEs from various origins have different activities under the same pH. Attentions should be imposed on this during the combinatorial biosynthesis in order to abtain the enzymes with the optimal bioactivities.