scholarly journals Heronapyrrole D: A case of co-inspiration of natural product biosynthesis, total synthesis and biodiscovery

2014 ◽  
Vol 10 ◽  
pp. 1228-1232 ◽  
Author(s):  
Jens Schmidt ◽  
Zeinab Khalil ◽  
Robert J Capon ◽  
Christian B W Stark
Keyword(s):  
Antibacterial Activity ◽  
Natural Products ◽  
Total Synthesis ◽  
Asymmetric Synthesis ◽  
Natural Product ◽  
Joint Effort ◽  
Natural Product Biosynthesis ◽  
New Members ◽  
Degree Of Oxidation ◽  
Rare Class

The heronapyrroles A–C have first been isolated from a marine-derived Streptomyces sp. (CMB-0423) in 2010. Structurally, these natural products feature an unusual nitropyrrole system to which a partially oxidized farnesyl chain is attached. The varying degree of oxidation of the sesquiterpenyl subunit in heronapyrroles A–C provoked the hypothesis that there might exist other hitherto unidentified metabolites. On biosynthetic grounds a mono-tetrahydrofuran-diol named heronapyrrole D appeared a possible candidate. We here describe a short asymmetric synthesis of heronapyrrole D, its detection in cultivations of CMB-0423 and finally the evaluation of its antibacterial activity. We thus demonstrate that biosynthetic considerations and the joint effort of synthetic and natural product chemists can result in the identification of new members of a rare class of natural products.

scholarly journals Total Synthesis of the Reported Structure of Cahuitamycin A

2020 ◽  
Author(s):  
Justin Shapiro ◽  
Savannah Post ◽  
William Wuest
Keyword(s):  
Natural Products ◽  
Total Synthesis ◽  
Natural Product ◽  
Twelve Step ◽  
Target Compound ◽  
New Family ◽  
Iron Trafficking ◽  
Linear Sequence ◽  
Alternative Structure ◽  
Synthetic Target

In a 2016 screen of natural product extracts a new family of natural products, the cahuitamycins, was discovered and found to inhibit the formation of biofilms in the human pathogen <i>Acinetobacter baumannii</i>. The molecules contain an unusual piperazate residue that raises structure/function and biosynthesis questions and resemble iron-trafficking virulence factors from <i>A. baumannii</i>, suggesting a connection between metal homeostasis and biofilm-mediated pathogenicity. Here we disclose the first total synthesis of the reported structure of cahuitamycin A in a twelve-step longest linear sequence and 18% overall yield. Comparison of spectral data of the authentic natural product and synthetic target compound demonstrate that the reported structure is distinct from the isolated metabolite. Herein, we propose an alternative structure to reconcile our findings with the isolation report, setting the stage for future synthetic and biochemical investigations of an important class of natural products.

scholarly journals Synthetic study of ravidomycin, a hybrid natural product

2000 ◽  
Vol 72 (9) ◽  
pp. 1783-1786 ◽  
Author(s):  
Keisuke Suzuki
Keyword(s):  
Natural Products ◽  
Total Synthesis ◽  
Natural Product ◽  
Amino Sugar ◽  
Antitumor Antibiotics ◽  
Ready Availability ◽  
Silyl Acetals ◽  
Gilvocarcin V ◽  
Absolute Stereochemistry

Strategies and tactics associated with the total synthesis of hybrid natural products are discussed. The target is ravidomycin (2), one of the gilvocarcin-class antitumor antibiotics with an aryl C-glycoside structure. The first total synthesis of 2, which was achieved along similar lines of that of gilvocarcin V (1), served for the determination of the relative as well as the absolute stereochemistry of 2. Also revealed was a limitation of the synthetic scheme so long as the amino sugar congener was concerned. A preliminary result is discussed on the [2+2+2] approach that relies on the ready availability of various benzocyclobutene derivatives via regioselective [2+2] cycloaddition of α-alkoxybenzynes and ketene silyl acetals.

scholarly journals Harnessing the biocatalytic potential of iron- and α-ketoglutarate-dependent dioxygenases in natural product total synthesis

2020 ◽  
Vol 37 (8) ◽  
pp. 1065-1079 ◽  
Author(s):  
Christian R. Zwick ◽  
Hans Renata
Keyword(s):  
Natural Products ◽  
Total Synthesis ◽  
Natural Product ◽  
Oxidative Transformations

This review highlights recent chemoenzymatic syntheses of natural products that feature strategic applications of oxidative transformations with Fe/αKG enzymes.

scholarly journals mSphere of Influence: Synthetic Biology of Natural Product Biosynthesis

mSphere ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Mark C. Walker
Keyword(s):  
Natural Products ◽  
Synthetic Biology ◽  
Natural Product ◽  
Gene Cluster ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene ◽  
Natural Product Biosynthesis ◽  
Antibiotic Compounds ◽  
Approaches To Study

ABSTRACT Mark Walker studies the biosynthesis and engineering of bacterial natural products with the long-term goal of identifying new antibiotic compounds. In this mSphere of Influence, he reflects on how “Direct cloning and refactoring of a silent lipopeptide biosynthetic gene cluster yields the antibiotic taromycin A” by K. Yamanaka, K. A. Reynolds, R. D. Kersten, K. S. Ryan, et al. (Proc Natl Acad Sci USA 111:1957–1962, 2014, https://doi.org/10.1073/pnas.1319584111) impacted his thinking on using synthetic biology approaches to study natural product biosynthesis.

Evolutionary dynamics of natural product biosynthesis in bacteria

2020 ◽  
Vol 37 (4) ◽  
pp. 566-599 ◽  
Author(s):  
Marc G. Chevrette ◽  
Karina Gutiérrez-García ◽  
Nelly Selem-Mojica ◽  
César Aguilar-Martínez ◽  
Alan Yañez-Olvera ◽  
...  
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Evolutionary Dynamics ◽  
Chemical Diversity ◽  
Enzyme Promiscuity ◽  
Evolutionary Mechanisms ◽  
Natural Product Biosynthesis ◽  
Metabolic Traits

We review known evolutionary mechanisms underlying the overwhelming chemical diversity of bacterial natural products biosynthesis, focusing on enzyme promiscuity and the evolution of enzymatic domains that enable metabolic traits.

Recent advances in the synthesis of oxaspirolactones and their application in the total synthesis of related natural products

2019 ◽  
Vol 17 (31) ◽  
pp. 7270-7292 ◽  
Author(s):  
Sagar S. Thorat ◽  
Ravindar Kontham
Keyword(s):  
Natural Products ◽  
Total Synthesis ◽  
Natural Product ◽  
Medicinal Chemistry ◽  
Natural Product Chemistry ◽  
Structural Motifs ◽  
Recent Advances ◽  
Synthetic Molecules ◽  
Product Chemistry

Oxaspirolactones are ubiquitous structural motifs found in natural products and synthetic molecules with a diverse biochemical and physicochemical profile, and represent a valuable target in natural product chemistry and medicinal chemistry.

scholarly journals Toward Biosynthetic Design and Implementation of Escherichia coli-Derived Paclitaxel and Other Heterologous Polyisoprene Compounds

2012 ◽  
Vol 78 (8) ◽  
pp. 2497-2504 ◽  
Author(s):  
Ming Jiang ◽  
Gregory Stephanopoulos ◽  
Blaine A. Pfeifer
Keyword(s):  
Escherichia Coli ◽  
Natural Products ◽  
Natural Product ◽  
Cellular Metabolism ◽  
Compound Formation ◽  
Natural Product Biosynthesis ◽  
Content Type ◽  
E Coli ◽  
Design And Implementation ◽  
Final Compound

ABSTRACTEscherichia colioffers unparalleled engineering capacity in the context of heterologous natural product biosynthesis. However, as with other heterologous hosts, cellular metabolism must be designed or redesigned to support final compound formation. This task is at once complicated and aided by the fact that the cell does not natively produce an abundance of natural products. As a result, the metabolic engineer avoids complicated interactions with native pathways closely associated with the outcome of interest, but this convenience is tempered by the need to implement the required metabolism to allow functional biosynthesis. This review focuses on engineeringE. colifor the purpose of polyisoprene formation, as it is related to isoprenoid compounds currently being pursued through a heterologous approach. In particular, the review features the compound paclitaxel and early efforts to design and overproduce intermediates throughE. coli.

Genome-Guided Discovery of Natural Products and Biosynthetic Pathways from Australia’s Untapped Microbial Megadiversity

2016 ◽  
Vol 69 (2) ◽  
pp. 129 ◽  
Author(s):  
John A. Kalaitzis ◽  
Shane D. Ingrey ◽  
Rocky Chau ◽  
Yvette Simon ◽  
Brett A. Neilan
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Genome Sequencing ◽  
Dna Sequences ◽  
Gene Clusters ◽  
Biosynthetic Pathways ◽  
Natural Product Biosynthesis ◽  
Guided Discovery ◽  
Biosynthesis Gene ◽  
Microbial Natural Products

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.

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