Article

Reconstruction of a bacterial isoprenoid biosynthetic pathway in Saccharomyces cerevisiae

Center for Microbial Biotechnology, DTU-Biosys, Building 223, 2800 Kgs Lyngby, Denmark.
FEBS Letters (Impact Factor: 3.34). 12/2008; 582(29):4032-8. DOI: 10.1016/j.febslet.2008.10.045
Source: PubMed

ABSTRACT A eukaryotic mevalonate pathway transferred and expressed in Escherichia coli, and a mammalian hydrocortisone biosynthetic pathway rebuilt in Saccharomyces cerevisiae are examples showing that transferring metabolic pathways from one organism to another can have a powerful impact on cell properties. In this study, we reconstructed the E. coli isoprenoid biosynthetic pathway in S. cerevisiae. Genes encoding the seven enzymatic steps of the pathway were cloned and expressed in S. cerevisiae. mRNA from the seven genes was detected, and the pathway was shown able to sustain growth of yeast in conditions of inhibition of its constitutive isoprenoid biosynthetic pathway.

0 Followers
 · 
138 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: : Microbial production of isoprenoids provides an attractive alternative to biomass extraction and chemical synthesis. Although widespread research aims for isoprenoid biosynthesis, it is still in its infancy in terms of delivering commercial products. Large barriers remain in realizing a cost-competitive process, for example, developing an optimal microbial cell factory. Here, we summarize the many tools and methods that have been developed in the metabolic engineering of isoprenoid production, with the advent of systems biology and synthetic biology, and discuss how these technologies advance to accelerate the design-build-test engineering cycle to obtain optimum microbial systems. It is anticipated that innovative combinations of new and existing technologies will continue to emerge, which will enable further development of microbial cell factories for commercial isoprenoid production.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Monoclonal antibodies (mAbs) and antibody fragments represent the most important biopharmaceutical products today. Because full length antibodies are glycosylated, mammalian cells, which allow human-like N-glycosylation, are currently used for their production. However, mammalian cells have several drawbacks when it comes to bioprocessing and scale-up, resulting in long processing times and elevated costs. By contrast, antibody fragments, that are not glycosylated but still exhibit antigen binding properties, can be produced in microbial organisms, which are easy to manipulate and cultivate. In this review, we summarize recent advances in the expression systems, strain engineering, and production processes for the three main microbials used in antibody and antibody fragment production, namely Saccharomyces cerevisiae, Pichia pastoris, and Escherichia coli.
    Trends in Biotechnology 10/2013; 32(1). DOI:10.1016/j.tibtech.2013.10.002 · 10.04 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Artemisinic acid, an amorphane sesquiterpene, is isolated from Artemisia annua L. Although having less efficacy than artemisinin, artemisinic acid has a variety of pharmacological activity, such as antimalarial activity, anti-tumor activity, antipyretic effect, antibacterial activity, allelopathy effect and anti-adipogenesis effect. This development has drastically increased artemisinic acid demand worldwide. Although many approaches, namely extraction of artemisinic acid from A.annua L, in vitro production of artemisinic acid by cell and tissue culture, total chemical synthesis and fermentation production by use of synthetic biology technology can improve artemisinic acid production, A.annua L. is currently the only commercial source for the artemisinic acid supply in the international market. Recently tremendous advances, however, demonstrate that the production of artemisinic acid in microorganisms and further semi-synthesis to artemisinin is a feasible complementary strategy that would help reduce artemisinin cost in the future. 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. This review, therefore, covers the recent developments related to the physico-chemical properties of artemisinic acid, bioactivity of this important molecular, solvent extraction strategies and chemical analysis, and highlights a scale production of artemisinic acid by synthetic biology and the relevant enzymes and genes. In the end the status of artemisinic acid in the biosynthesis pathway of artemisinin is discussed in detail. Together these results provide a synopsis of a more global view of artemisinic acid than previously available.
    RSC Advances 05/2013; 3(21):7622-7641. DOI:10.1039/C3RA40525G · 3.71 Impact Factor

Full-text (2 Sources)

Download
44 Downloads
Available from
May 22, 2014