scholarly journals Cell factory engineering for improved production of natural products

2019 ◽  
Vol 36 (9) ◽  
pp. 1233-1236 ◽  
Author(s):  
Jens Nielsen
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Cell Factory ◽  
Primary Metabolism ◽  
Natural Product Biosynthesis

Natural product biosynthesis is inherently linked with the primary metabolism in terms of providing precursors and co-factors.

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.

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.

scholarly journals Following evolution's lead to a single residue switch for diterpene synthase product outcome

2007 ◽  
Vol 104 (18) ◽  
pp. 7397-7401 ◽  
Author(s):  
Meimei Xu ◽  
P. Ross Wilderman ◽  
Reuben J. Peters
Keyword(s):  
Natural Products ◽  
Higher Plants ◽  
Primary Metabolism ◽  
Terpene Synthases ◽  
Natural Product Biosynthesis ◽  
Widespread Occurrence ◽  
Gibberellin Metabolism ◽  
Diterpene Synthase ◽  
Short Circuits ◽  
Product Outcome

There have been few insights into the biochemical origins of natural product biosynthesis from primary metabolism. Of particular interest are terpene synthases, which often mediate the committed step in particular biosynthetic pathways so that alteration of their product outcome is a key step in the derivation of novel natural products. These enzymes also catalyze complex reactions of significant mechanistic interest. Following an evolutionary lead from two recently diverged, functionally distinct diterpene synthase orthologs from different subspecies of rice, we have identified a single residue that can switch product outcome. Specifically, the mutation of a conserved isoleucine to threonine that acts to convert not only the originally targeted isokaurene synthase into a specific pimaradiene synthase but also has a much broader effect, which includes conversion of the ent-kaurene synthases found in all higher plants for gibberellin phytohormone biosynthesis to the production of pimaradiene. This surprisingly facile switch for diterpene synthase catalytic specificity indicates the ease with which primary (gibberellin) metabolism can be subverted to secondary biosynthesis and may underlie the widespread occurrence of pimaradiene-derived natural products. In addition, because this isoleucine is required for the mechanistically more complex cyclization to tetracyclic kaurene, whereas substitution with threonine “short-circuits” this mechanism to produce the “simpler” tricyclic pimaradiene, our results have some implications regarding the means by which terpene synthases specify product outcome.

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 Cytochromes P450 for natural product biosynthesis in Streptomyces: sequence, structure, and function

2017 ◽  
Vol 34 (9) ◽  
pp. 1141-1172 ◽  
Author(s):  
Jeffrey D. Rudolf ◽  
Chin-Yuan Chang ◽  
Ming Ma ◽  
Ben Shen
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Cytochromes P450 ◽  
Structure And Function ◽  
Sequence Structure ◽  
Natural Product Biosynthesis ◽  
And Function

This review catalogues functionally characterized P450s fromStreptomycesand discusses their sequences, structures, and functions in natural products biosynthesis.

scholarly journals Generation of two New Macrolactones through Sequential Biotransformation of Dihydroresorcylide

2011 ◽  
Vol 6 (2) ◽  
pp. 1934578X1100600
Author(s):  
Jia Zeng ◽  
Jonathan Valiente ◽  
Jixun Zhan
Keyword(s):  
Escherichia Coli ◽  
Natural Products ◽  
Natural Product ◽  
Beauveria Bassiana ◽  
Natural Product Biosynthesis ◽  
Whole Cell ◽  
E Coli ◽  
Escherichia Coli Bl21 ◽  
Engineered Escherichia Coli

Biotransformation is an effective method to generate new derivatives from natural products. Combination of various enzymes or whole-cell biocatalysts creates new opportunities for natural product biosynthesis. Dihydroresorcylide (1) is a phytotoxic macrolactone from Acremonium aeae. It was first chlorinated at C-11 by an engineered Escherichia coli BL21-CodonPlus (DE3)-RIL/pJZ54 strain that overexpresses a fungal flavin-dependent halogenase, and subsequently glycosylated at 12-OH by Beauveria bassiana ATCC 7159, giving rise to a novel derivative, 11-chloro-4′- O-methyl-12- O-β-D-glucosyl-dihydroresorcylide (3). Although 1 can be converted into a new 4′- O-methyl-glucosylated derivative 4 by B. bassiana, this product cannot be further chlorinated by E. coli BL21-CodonPlus (DE3)-RIL/pJZ54 to afford 3. The sequence of these two biotransformation steps was thus restricted and not interchangeable. This sequential biotransformation approach can be applied to other structurally similar natural products to create novel derivatives.

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