Content area
Full Text
Appl Biochem Biotechnol (2012) 167:11721182
DOI 10.1007/s12010-012-9583-1
Rama Raju Baadhe & Naveen Kumar Mekala &
Satwik Reddy Palagiri & Sreenivasa Rao Parcha
Received: 31 October 2011 /Accepted: 20 January 2012 / Published online: 15 February 2012# Springer Science+Business Media, LLC 2012
Abstract In this case study, we designed a farnesyl pyrophosphate (FPP) biosynthetic network using hybrid functional Petri net with extension (HFPNe) which is derived from traditional Petri net theory and allows easy modeling with graphical approach of various types of entities in the networks together. Our main objective is to improve the production of FPP in yeast, which is further converted to amorphadiene (AD), a precursor of artemisinin (antimalarial drug). Natively, mevalonate (MEV) pathway is present in yeast. Methyl erythritol phosphate pathways (MEP) are present only in higher plant plastids and eubacteria, but not present in yeast. IPP and DAMP are common isomeric intermediate in these two pathways, which immediately yields FPP. By integrating these two pathways in yeast, we augmented the FPP synthesis approximately two folds higher (431.16 U/pt) than in MEV pathway alone (259.91 U/pt) by using HFPNe technique. Further enhanced FPP levels converted to AD by amorphadiene synthase gene yielding 436.5 U/pt of AD which approximately two folds higher compared to the AD (258.5 U/pt) synthesized by MEV pathway exclusively. Simulation and validation processes performed using these models are reliable with identified biological information and data.
Keywords Amorpha diene . Artemisinin . Farnesyl pyrophosphate . Hybrid functional Petri net with extensions . Methylerythritol phosphate pathway . Mevalonate Pathway
Abbreviations
AD AmorphadieneHFPNe Hybrid functional Petri net with extension MEV MevalonateMEP Methylerithritol 4-phosphate
R. R. Baadhe (*) : N. K. Mekala : S. R. Parcha
Department of Biotechnology, National Institute of Technology, Warangal, India e-mail: [email protected]
S. R. Palagiri
Arkabio Research Technologies, Hyderabad, India
Development of Petri Net-Based Dynamic Modelfor Improved Production of Farnesyl Pyrophosphate by Integrating Mevalonate and Methylerythritol Phosphate Pathways in Yeast
Appl Biochem Biotechnol (2012) 167:11721182 1173
FPP Farnesyl pyrophosphate
IPP Isopentenyl pyrophosphateDMAPP Dimethylallyl pyrophosphateGPP Geranyl pyrophosphate
Introduction
Over the last few years, usage of terpenoids has increased exponentially in medicine and aromatics. They offer a viable commercial alternative to chemically synthesized products of similar use. Terpenoids are typically extracted from plants [1] and microorganisms. Terpenoids, being secondary metabolites, produced...