New chemistry from natural product biosynthesis

2016 ◽  
Vol 44 (3) ◽  
pp. 738-744 ◽  
Author(s):  
Catherine B. Hubert ◽  
Sarah M. Barry

Catalysts are a vital part of synthetic chemistry. However, there are still many important reactions for which catalysts have not been developed. The use of enzymes as biocatalysts for synthetic chemistry is growing in importance due to the drive towards sustainable methods for producing both bulk chemicals and high value compounds such as pharmaceuticals, and due to the ability of enzymes to catalyse chemical reactions with excellent stereoselectivity and regioselectivity. Such challenging transformations are a common feature of natural product biosynthetic pathways. In this mini-review, we discuss the potential to use biosynthetic pathways as a starting point for biocatalyst discovery. We introduce the reader to natural product assembly and tailoring, then focus on four classes of enzyme that catalyse C─H bond activation reactions to functionalize biosynthetic precursors. Finally, we briefly discuss the challenges involved in novel enzyme discovery.

2018 ◽  
Vol 35 (8) ◽  
pp. 707-720 ◽  
Author(s):  
Susan C. Wang

This highlight examines the functions of cobalamin-dependent radicalS-adenosyl-l-methionine enzymes that catalyse chemically-challenging reactions in several bacterial natural product biosynthetic pathways.


2016 ◽  
Vol 69 (2) ◽  
pp. 129 ◽  
Author(s):  
John A. Kalaitzis ◽  
Shane D. Ingrey ◽  
Rocky Chau ◽  
Yvette Simon ◽  
Brett A. Neilan

Historically microbial natural product biosynthesis pathways were elucidated mainly by isotope labelled precursor directed feeding studies. Now the genetics underpinning the assembly of microbial natural products biosynthesis is so well understood that some pathways and their products can be predicted from DNA sequences alone. The association between microbial natural products and their biosynthesis gene clusters is now driving the field of ‘genetics guided natural product discovery’. This account overviews our research into cyanotoxin biosynthesis before the genome sequencing era through to some recent discoveries resulting from the mining of Australian biota for natural product biosynthesis pathways.


F1000Research ◽  
2016 ◽  
Vol 4 ◽  
pp. 1399 ◽  
Author(s):  
Gao-Yi Tan ◽  
Zixin Deng ◽  
Tiangang Liu

With the successful production of artemisinic acid in yeast, the promising potential of synthetic biology for natural product biosynthesis is now being realized. The recent total biosynthesis of opioids in microbes is considered to be another landmark in this field. The importance and significance of enzymes in natural product biosynthetic pathways have been re-emphasized by these advancements. Therefore, the characterization and elucidation of enzymatic function in natural product biosynthesis are undoubtedly fundamental for the development of new drugs and the heterologous biosynthesis of active natural products. Here, discoveries regarding enzymatic function in natural product biosynthesis over the past year are briefly reviewed.


F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 1399 ◽  
Author(s):  
Gao-Yi Tan ◽  
Zixin Deng ◽  
Tiangang Liu

With the successful production of artemisinic acid in yeast, the promising potential of synthetic biology for natural product biosynthesis is now being realized. The recent total biosynthesis of opioids in microbes is considered to be another landmark in this field. The importance and significance of enzymes in natural product biosynthetic pathways have been re-emphasized by these advancements. Therefore, the characterization and elucidation of enzymatic function in natural product biosynthesis are undoubtedly fundamental for the development of new drugs and the heterologous biosynthesis of active natural products. Here, discoveries regarding enzymatic function in natural product biosynthesis over the past year are briefly reviewed.


Biochemistry ◽  
2020 ◽  
Vol 59 (51) ◽  
pp. 4787-4792
Author(s):  
Takuma Matsushita ◽  
Shinji Kishimoto ◽  
Kodai Hara ◽  
Hiroshi Hashimoto ◽  
Kenji Watanabe

2021 ◽  
Author(s):  
Sofie Dekimpe ◽  
Joleen Masschelein

Condensation domains perform highly diverse functions during natural product biosynthesis and are capable of generating remarkable chemical diversity.


Synlett ◽  
2019 ◽  
Vol 30 (11) ◽  
pp. 1289-1302 ◽  
Author(s):  
Phil Servatius ◽  
Lukas Junk ◽  
Uli Kazmaier

Peptide modifications via C–C bond formation have emerged as valuable tools for the preparation and alteration of non-proteinogenic amino acids and the corresponding peptides. Modification of glycine subunits in peptides allows for the incorporation of unusual side chains, often in a highly stereoselective manner, orchestrated by the chiral peptide backbone. Moreover, modifications of peptides are not limited to the peptidic backbone. Many side-chain modifications, not only by variation of existing functional groups, but also by C–H functionalization, have been developed over the past decade. This account highlights the synthetic contributions made by our group and others to the field of peptide modifications and their application in natural product syntheses.1 Introduction2 Peptide Backbone Modifications via Peptide Enolates2.1 Chelate Enolate Claisen Rearrangements2.2 Allylic Alkylations2.3 Miscellaneous Modifications3 Side-Chain Modifications3.1 C–H Activation3.1.1 Functionalization via Csp3–H Bond Activation3.2.2 Functionalization via Csp2–H Bond Activation3.2 On Peptide Tryptophan Syntheses4 Conclusion


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