Journal ArticleDOI
Expression of a synthetic Artemesia annua amorphadiene synthase in Aspergillus nidulans yields altered product distribution
David Lubertozzi,Jay D. Keasling +1 more
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TLDR
The results indicate that the host environment can greatly impact the terpenes produced from terpene synthase, as well as the transformants normally produced as minor by-products in planta.Abstract:
A gene encoding a plant terpene cyclase, Artemisia annua amorpha-4,11-diene synthase (ADS), was expressed in Aspergillus nidulans under control of a strong constitutive promoter, (p)gpdA. The transformants produced only small amounts of amorphadiene, but much larger amounts of similar sesquiterpenes normally produced as minor by-products in planta. In contrast, expression of ADS in Escherichia coli produced almost exclusively amorpha-4,11-diene. These results indicate that the host environment can greatly impact the terpenes produced from terpene synthases.read more
Citations
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Six novel constitutive promoters for metabolic engineering of Aspergillus niger
TL;DR: Product titers from the detection limit to up to 570 mg/L proved that the set of constitutive promoters is a powerful tool for the fine-tuning of metabolic pathways for the improvement of industrial production processes.
Journal ArticleDOI
Functional expression of an orchid fragrance gene in Lactococcus lactis.
Adelene Ai-Lian Song,Janna Ong Abdullah,Mohd Puad Abdullah,Norazizah Shafee,Raha Abdul Rahim +4 more
TL;DR: Vanda Mimi Palmer (VMP), an orchid hybrid of Vanda tesselata and Vanda Tan Chay Yan is a highly scented tropical orchid which blooms all year round is found to be a suitable host for the characterization of plant terpene synthases.
Journal ArticleDOI
Artemisinic acid: A promising molecule potentially suitable for the semi-synthesis of artemisinin
TL;DR: The key genes encoding for enzymes regulating the biosynthesis of artemisnic acid in planta are fully understood to enable metabolic engineering of the pathway, and results from pilot genetic engineering studies in microbial strains thus far are very inspiring.
Journal ArticleDOI
Metabolic engineering of plants for artemisinin synthesis
TL;DR: The efforts taken to enhance artemisinin production in A. annua via transgenesis are described and the need to apply state-of-the-art synthetic biology approaches to ensure successful biosynthesis of the drug is emphasized.
Journal ArticleDOI
Optimization of genetic transformation of Artemisia annua L. Using Agrobacterium for Artemisinin production
TL;DR: The Agrobacterium tumefaciens AGl1 strain was the most effective to be transformed in to A. annua than GV3101 and LBA4404 strain and the effect of organosilicone surfactants produced the highest efficiency of transformation.
References
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Journal ArticleDOI
Production of the antimalarial drug precursor artemisinic acid in engineered yeast
Dae-Kyun Ro,Eric M. Paradise,Mario Ouellet,Karl Fisher,Karyn L. Newman,John M. Ndungu,Ho Kimberly,Eachus Rachel,Timothy S. Ham,James Kirby,Michelle C. Y. Chang,Sydnor T. Withers,Yoichiro Shiba,Richmond Sarpong,Jay D. Keasling +14 more
TL;DR: The engineering of Saccharomyces cerevisiae to produce high titres (up to 100 mg l-1) of artemisinic acid using an engineered mevalonate pathway, amorphadiene synthase, and a novel cytochrome P450 monooxygenase from A. annua that performs a three-step oxidation of amorpha-4,11-diene to art Artemisinic acid.
Journal ArticleDOI
Engineering a mevalonate pathway in Escherichia coli for production of terpenoids
TL;DR: The strains developed in this study can serve as platform hosts for the production of any terpenoid compound for which a terpene synthase gene is available, and are the universal precursors to all isoprenoids.
Journal ArticleDOI
Designed divergent evolution of enzyme function.
TL;DR: The construction of seven specific and active synthases that use different reaction pathways to produce the specific and very different products is presented, demonstrating the feasibility of exploiting the underlying evolvability of this scaffold and providing evidence that rational approaches based on these ideas are useful for enzyme design.
Journal ArticleDOI
Targeting angiogenesis with a conjugate of HPMA copolymer and TNP-470
Ronit Satchi-Fainaro,Mark Puder,John W. Davies,Hai T Tran,David A. Sampson,Arin K. Greene,Gabriel Corfas,Judah Folkman +7 more
TL;DR: A water-soluble conjugate of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer, Gly-Phe-Leu-Gly linker and T NP-470 substantially enhanced and prolonged the activity of TNP-470 in vivo in tumor and hepatectomy models.
Journal ArticleDOI
High-level production of amorpha-4,11-diene in a two-phase partitioning bioreactor of metabolically engineered Escherichia coli.
Jack D. Newman,Jessica Marshall,Michelle C. Y. Chang,Farnaz Nowroozi,Eric M. Paradise,Douglas J. Pitera,Karyn L. Newman,Jay D. Keasling +7 more
TL;DR: This work reports on a strain of Escherichia coli containing a heterologous, nine‐gene biosynthetic pathway for the production of the terpene amorpha‐4,11‐diene, a precursor to the anti‐malarial drug artemisinin, and shows that amorphadiene evaporates from a fermentor with a half‐life of about 50 min.