Faculty Opinions recommendation of Optimizing natural products by biosynthetic engineering: discovery of nonquinone Hsp90 inhibitors.

Author(s):  
Peter Wipf
2008 ◽  
Vol 51 (18) ◽  
pp. 5494-5497 ◽  
Author(s):  
Ming-Qiang Zhang ◽  
Sabine Gaisser ◽  
Mohammad Nur-E-Alam ◽  
Lesley S. Sheehan ◽  
William A. Vousden ◽  
...  

Author(s):  
Takayoshi Awakawa ◽  
Lena Barra ◽  
Ikuro Abe

Abstract Sulfonamides and sulfamates are a group of organosulfur compounds that contain the signature sulfamoyl structural motif. These compounds were initially only known as synthetic antibacterial drugs but were later also discovered as natural products. Eight highly potent examples have been isolated from actinomycetes to date, illustrating the large biosynthetic repertoire of this bacterial genus. For the biosynthesis of these compounds, several distinct and unique biosynthetic machineries have been discovered, capable to generate the unique S-N bond. For the creation of novel, second generation natural products by biosynthetic engineering efforts, a detailed understanding of the underlying enzyme machinery towards potent structural motifs is crucial. In this review, we aim to summarize the current state of knowledge on sulfonamide and sulfamate biosynthesis. A detailed discussion for the secondary sulfamate ascamycin, the tertiary sulfonamide sulfadixiamycin A, and the secondary sulfonamide SB-203208 is provided and their bioactivities and mode of actions are discussed.


2014 ◽  
Vol 33 (8) ◽  
pp. 495-502
Author(s):  
Jian-Min Jia ◽  
Fang Liu ◽  
Xiao-Li Xu ◽  
Xiao-Ke Guo ◽  
Fen Jiang ◽  
...  

2016 ◽  
Vol 33 ◽  
pp. 67-75 ◽  
Author(s):  
Alessandra S. Eustáquio ◽  
Li-Ping Chang ◽  
Greg L. Steele ◽  
Christopher J. O׳Donnell ◽  
Frank E. Koehn

2009 ◽  
Vol 81 (6) ◽  
pp. 1065-1074 ◽  
Author(s):  
Jason Micklefield

Biosynthetic engineering involves the reprogramming of genes that are involved in the biosynthesis of natural products to generate new "non-natural" products, which might otherwise not exist in nature. Potentially this approach can be used to provide large numbers of secondary metabolites variants, with altered biological activities, many of which are too complex for effective total synthesis. Recently we have been investigating the biosynthesis of the calcium-dependent antibiotics (CDAs) which are members of the therapeutically relevant class of acidic lipopeptide antibiotics. CDAs are assembled by nonribosomal peptide synthetase (NRPS) enzymes. These large modular assembly-line enzymes process intermediates that are covalently tethered to peptidyl carrier protein (PCP) domain bonds bonds, which makes them particularly amenable to reprogramming. The CDA producer, Streptomyces coelicolor, is also a genetically tractable model organism which makes CDA an ideal template for biosynthetic engineering. To this end we have elucidated many of the key steps in CDA biosynthesis and utilized this information to develop methods that have enabled the engineered biosynthesis of wide range of CDA-type lipopeptides.


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