Journal ArticleDOI
Strain improvement of recombinant Escherichia coli for efficient production of plant flavonoids.
Effendi Leonard,Yajun Yan,Zachary Fowler,Zhen Li,Chin Giaw Lim,Kok Hong Lim,Mattheos A. G. Koffas +6 more
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TLDR
E. coli strains capable of high-level flavonoid synthesis through traditional metabolic engineering techniques are developed and demonstrated the efficient and scalable production of plant flavonoids from E. coli for pharmaceutical and nutraceutical applications.Abstract:
Plant flavonoid polyphenols continue to find increasing pharmaceutical and nutraceutical applications; however their isolation, especially of pure compounds, from plant material remains an underlying challenge. In the past Escherichia coli, one of the most well-characterized microorganisms, has been utilized as a recombinant host for protein expression and heterologous biosynthesis of small molecules. However, in many cases the expressed protein activities and biosynthetic efficiency are greatly limited by the host cellular properties, such as precursor and cofactor availability and protein or product tolerance. In the present work, we developed E. coli strains capable of high-level flavonoid synthesis through traditional metabolic engineering techniques. In addition to grafting the plant biosynthetic pathways, the methods included engineering of an alternative carbon assimilation pathway and the inhibition of competitive reaction pathways in order to increase intracellular flavonoid backbone precursors a...read more
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Chemistry and Biological Activities of Flavonoids: An Overview
Shashank Kumar,Abhay K. Pandey +1 more
TL;DR: The structural features of flavonoids, their beneficial roles in human health, and significance in plants as well as their microbial production are highlighted.
Journal ArticleDOI
An Engineered Microbial Platform for Direct Biofuel Production from Brown Macroalgae
Adam J. Wargacki,Effendi Leonard,Maung Nyan Win,Drew D. Regitsky,Christine Nicole S. Santos,Peter B Kim,Susan Rudd Cooper,Ryan M. Raisner,Asael Herman,Alicia B. Sivitz,Arun Lakshmanaswamy,Yuki Kashiyama,David Baker,Yasuo Yoshikuni +13 more
TL;DR: A 36–kilo–base pair DNA fragment from Vibrio splendidus encoding enzymes for alginate transport and metabolism is presented, and a genomic integration of this ensemble generated a microbial platform that can simultaneously degrade, uptake, and metabolizeAlginate.
Journal ArticleDOI
Synthetic biology for the directed evolution of protein biocatalysts: navigating sequence space intelligently
TL;DR: Improving enzymes by directed evolution requires the navigation of very large search spaces; this work surveys how to do this intelligently.
Journal ArticleDOI
Genome-scale metabolic network modeling results in minimal interventions that cooperatively force carbon flux towards malonyl-CoA.
TL;DR: Combined effect of the genetic interventions was found to be synergistic based on a developed analysis method that correlates genetic modification to cell phenotype, specifically the identified knockout targets and overexpression targets can cooperatively force carbon flux towards malonyl-CoA.
References
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Journal ArticleDOI
One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products
TL;DR: A simple and highly efficient method to disrupt chromosomal genes in Escherichia coli in which PCR primers provide the homology to the targeted gene(s), which should be widely useful, especially in genome analysis of E. coli and other bacteria.
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Flavonoid Biosynthesis. A Colorful Model for Genetics, Biochemistry, Cell Biology, and Biotechnology
TL;DR: The role of flavonoids as the major red, blue, and purple pigments in plants has gained these secondary products a great deal of attention over the years.
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Dietary cyanidin 3-O-beta-D-glucoside-rich purple corn color prevents obesity and ameliorates hyperglycemia in mice.
TL;DR: The results suggest that dietary PCC may ameliorate HF diet-induced insulin resistance in mice and provide a biochemical and nutritional basis for the use of PCC or anthocyanins as a functional food factor that may have benefits for the prevention of obesity and diabetes.
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Crystal Structures of Human Cytochrome P450 3A4 Bound to Metyrapone and Progesterone
Pamela A. Williams,Jose Cosme,Dijana Matak Vinkovic,Alison Ward,Hayley C. Angove,Philip J. Day,Clemens Vonrhein,Ian J. Tickle,Harren Jhoti +8 more
TL;DR: The structures revealed a surprisingly small active site, with little conformational change associated with the binding of either compound, and an unexpected peripheral binding site is identified, located above a phenylalanine cluster, which may be involved in the initial recognition of substrates or allosteric effectors.
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Different polyphenolic components of soft fruits inhibit α-amylase and α-glucosidase
TL;DR: In this paper, polyphenol-rich extracts from soft fruits were tested for their ability to inhibit alpha-amylase and alpha-glucosidase and there was a 10-fold difference between the least and most effective extracts.