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.

Beyond peptide bond formation: the versatile role of condensation domains in natural product biosynthesis

2021 ◽  
Author(s):  
Sofie Dekimpe ◽  
Joleen Masschelein
Keyword(s):  
Natural Product ◽  
Bond Formation ◽  
Peptide Bond ◽  
Chemical Diversity ◽  
Peptide Bond Formation ◽  
Natural Product Biosynthesis

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

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 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.

scholarly journals Biological and Chemical Diversity of Marine Sponge-Derived Microorganisms over the Last Two Decades from 1998 to 2017

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 853 ◽  
Author(s):  
Mei-Mei Cheng ◽  
Xu-Li Tang ◽  
Yan-Ting Sun ◽  
Dong-Yang Song ◽  
Yu-Jing Cheng ◽  
...  
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Natural Product ◽  
Marine Sponge ◽  
Marine Sponges ◽  
Chemical Diversity ◽  
Comprehensive Overview ◽  
Bioactive Secondary Metabolites ◽  
The Relationship ◽  
Product Chemistry

Marine sponges are well known as rich sources of biologically natural products. Growing evidence indicates that sponges harbor a wealth of microorganisms in their bodies, which are likely to be the true producers of bioactive secondary metabolites. In order to promote the study of natural product chemistry and explore the relationship between microorganisms and their sponge hosts, in this review, we give a comprehensive overview of the structures, sources, and activities of the 774 new marine natural products from sponge-derived microorganisms described over the last two decades from 1998 to 2017.

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.

Expansion of chemical space for natural products by uncommon P450 reactions

2017 ◽  
Vol 34 (9) ◽  
pp. 1061-1089 ◽  
Author(s):  
Xingwang Zhang ◽  
Shengying Li
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Protein Interactions ◽  
Chemical Space ◽  
Protein Protein Interactions ◽  
Natural Product Biosynthesis ◽  
Space Expansion

This review focuses on unusual P450 reactions related to new chemistry, skeleton construction, structure re-shaping, and protein–protein interactions in natural product biosynthesis, which play significant roles in chemical space expansion for natural products.

scholarly journals High-Throughput Screening Platform for Natural Product–Based Drug Discovery Against 3 Neglected Tropical Diseases

2014 ◽  
Vol 20 (1) ◽  
pp. 82-91 ◽  
Author(s):  
F. Annang ◽  
G. Pérez-Moreno ◽  
R. García-Hernández ◽  
C. Cordon-Obras ◽  
J. Martín ◽  
...  
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Natural Product ◽  
High Throughput ◽  
High Throughput Screening ◽  
Neglected Tropical Diseases ◽  
Chemical Diversity ◽  
Tropical Diseases ◽  
Isolation And Characterization ◽  
Microbial Extracts

African trypanosomiasis, leishmaniasis, and Chagas disease are 3 neglected tropical diseases for which current therapeutic interventions are inadequate or toxic. There is an urgent need to find new lead compounds against these diseases. Most drug discovery strategies rely on high-throughput screening (HTS) of synthetic chemical libraries using phenotypic and target-based approaches. Combinatorial chemistry libraries contain hundreds of thousands of compounds; however, they lack the structural diversity required to find entirely novel chemotypes. Natural products, in contrast, are a highly underexplored pool of unique chemical diversity that can serve as excellent templates for the synthesis of novel, biologically active molecules. We report here a validated HTS platform for the screening of microbial extracts against the 3 diseases. We have used this platform in a pilot project to screen a subset (5976) of microbial extracts from the MEDINA Natural Products library. Tandem liquid chromatography–mass spectrometry showed that 48 extracts contain potentially new compounds that are currently undergoing de-replication for future isolation and characterization. Known active components included actinomycin D, bafilomycin B1, chromomycin A3, echinomycin, hygrolidin, and nonactins, among others. The report here is, to our knowledge, the first HTS of microbial natural product extracts against the above-mentioned kinetoplastid parasites.

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