Polyketide Biosynthesis: The Erythromycin Example - Part 2: Impact of Genetics and Molecular Biology on Understanding and Engineering Erythromycin Biosynthesis (22:44)

SciVee ◽  
2009 ◽  
2001 ◽  
Vol 57 (4) ◽  
pp. 467-473 ◽  
Author(s):  
Dittmann E. ◽  
Neilan B. ◽  
Börner T.

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Edward Kalkreuter ◽  
Kyle S. Bingham ◽  
Aaron M. Keeler ◽  
Andrew N. Lowell ◽  
Jennifer J. Schmidt ◽  
...  

AbstractPolyketides, one of the largest classes of natural products, are often clinically relevant. The ability to engineer polyketide biosynthesis to produce analogs is critically important. Acyltransferases (ATs) of modular polyketide synthases (PKSs) catalyze the installation of malonyl-CoA extenders into polyketide scaffolds. ATs have been targeted extensively to site-selectively introduce various extenders into polyketides. Yet, a complete inventory of AT residues responsible for substrate selection has not been established, limiting the scope of AT engineering. Here, molecular dynamics simulations are used to prioritize ~50 mutations within the active site of EryAT6 from erythromycin biosynthesis, leading to identification of two previously unexplored structural motifs. Exchanging both motifs with those from ATs with alternative extender specificities provides chimeric PKS modules with expanded and inverted substrate specificity. Our enhanced understanding of AT substrate selectivity and application of this motif-swapping strategy are expected to advance our ability to engineer PKSs towards designer polyketides.


Author(s):  
Cecil E. Hall

The visualization of organic macromolecules such as proteins, nucleic acids, viruses and virus components has reached its high degree of effectiveness owing to refinements and reliability of instruments and to the invention of methods for enhancing the structure of these materials within the electron image. The latter techniques have been most important because what can be seen depends upon the molecular and atomic character of the object as modified which is rarely evident in the pristine material. Structure may thus be displayed by the arts of positive and negative staining, shadow casting, replication and other techniques. Enhancement of contrast, which delineates bounds of isolated macromolecules has been effected progressively over the years as illustrated in Figs. 1, 2, 3 and 4 by these methods. We now look to the future wondering what other visions are waiting to be seen. The instrument designers will need to exact from the arts of fabrication the performance that theory has prescribed as well as methods for phase and interference contrast with explorations of the potentialities of very high and very low voltages. Chemistry must play an increasingly important part in future progress by providing specific stain molecules of high visibility, substrates of vanishing “noise” level and means for preservation of molecular structures that usually exist in a solvated condition.


2020 ◽  
Vol 64 (6) ◽  
pp. 863-866
Author(s):  
Zhe Wu

Abstract The year 2019 marked the fortieth anniversary of the Chinese Society of Biochemistry and Molecular Biology (CSBMB), whose mission is to promote biomolecular research and education in China. The last 40 years have witnessed tremendous growth and achievements in biomolecular research by Chinese scientists and Essays in Biochemistry is delighted to publish this themed issue that focuses on exciting areas within RNA biology, with each review contributed by key experts from China.


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