scholarly journals The Logic, Experimental Steps, and Potential of Heterologous Natural Product Biosynthesis Featuring the Complex Antibiotic Erythromycin A Produced Through E. coli

10.3791/4346 ◽  
2013 ◽  
Author(s):  
Ming Jiang ◽  
Haoran Zhang ◽  
Blaine A. Pfeifer
Keyword(s):  
Natural Product ◽  
Natural Product Biosynthesis ◽  
E Coli ◽  
Erythromycin A

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.

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.

scholarly journals Efficient biosynthesis of nucleoside cytokinin angustmycin A containing an unusual sugar system

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Le Yu ◽  
Wenting Zhou ◽  
Yixuan She ◽  
Hongmin Ma ◽  
You-Sheng Cai ◽  
...  
Keyword(s):  
Natural Product ◽  
Glycosidic Bond ◽  
Natural Product Biosynthesis ◽  
E Coli ◽  
Cofactor Recycling ◽  
The Way

AbstractAngustmycin A has anti-mycobacterial and cytokinin activities, and contains an intriguing structure in which an unusual sugar with C5′-C6′ dehydration is linked to adenine via an N-glycosidic bond. However, the logic underlying the biosynthesis of this molecule has long remained obscure. Here, we address angustmycin A biosynthesis by the full deciphering of its pathway. We demonstrate that AgmD, C, A, E, and B function as d-allulose 6-phosphate 3-epimerase, d-allulose 6-phosphate pyrophosphokinase, adenine phosphoallulosyltransferase, phosphoribohydrolase, and phosphatase, respectively, and that these collaboratively catalyze the relay reactions to biosynthesize angustmycin C. Additionally, we provide evidence that AgmF is a noncanonical dehydratase for the final step to angustmycin A via a self-sufficient strategy for cofactor recycling. Finally, we have reconstituted the entire six-enzyme pathway in vitro and in E. coli leading to angustmycin A production. These results expand the enzymatic repertoire regarding natural product biosynthesis, and also open the way for rational and rapid discovery of other angustmycin related antibiotics.

Structural and Functional Analyses of a Spiro-Carbon-Forming, Highly Promiscuous Epoxidase from Fungal Natural Product Biosynthesis

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

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.

Mind the mushroom: natural product biosynthetic genes and enzymes of Basidiomycota

2021 ◽  
Author(s):  
Markus Gressler ◽  
Nikolai A. Löhr ◽  
Tim Schäfer ◽  
Stefanie Lawrinowitz ◽  
Paula Sophie Seibold ◽  
...  
Keyword(s):  
Natural Product ◽  
Biosynthetic Genes ◽  
Natural Product Biosynthesis

This article comprehensively reviews basidiomycete enzymes and their genes involved in natural product biosynthesis and primarily focuses on typical pathways and enzymes, along with the methods applied to investigate mushroom metabolism.

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