TITLE:
In-Silico Analysis & In-Vivo Results Concur on Glutathione Depletion in Glyphosate Resistant GMO Soy, Advancing a Systems Biology Framework for Safety Assessment of GMOs
AUTHORS:
V. A. Shiva Ayyadurai, Michael Hansen, John Fagan, Prabhakar Deonikar
KEYWORDS:
Glutathione, Genetic Modification, C1 Metabolism, Biomarker, Safety Assessment, In-Silico Analysis, Glyphosate, CytoSolve, Systems Biology, Safety Assessment
JOURNAL NAME:
American Journal of Plant Sciences,
Vol.7 No.12,
August
19,
2016
ABSTRACT: This study advances previous efforts towards development of computational
systems biology, in silico, methods for biosafety assessment
of genetically modified organisms (GMOs). C1 metabolism is a critical molecular
system in plants, fungi, and bacteria. In our previous research, critical molecular
systems of C1 metabolism were identified and modeled using CytoSolve?,
a platform for in silico analysis. In addition, multiple exogenous
molecular systems affecting C1 metabolism such as oxidative stress, shikimic acid
metabolism, glutathione biosynthesis, etc. were identified. Subsequent research
expanded the C1 metabolism computational models to integrate oxidative stress, suggesting
glutathione (GSH) depletion. Recent integration of data from the EPSPS genetic modification
of Soy, also known as Roundup Ready Soy (RRS), with C1 metabolism predicts similar
GSH depletion and HCHO accumulation in RRS. The research herein incorporates molecular
systems of glutathione biosynthesis and glyphosate catabolism to expand the extant in silico models of C1 metabolism. The in silico results predict
that Organic Soy will have a nearly 250% greater ratio of GSH and GSSG, a measure
of glutathione levels, than in RRS that are glyphosate-treated glyphosate-resistant
Soy versus the Organic Soy. These predictions also concur with in vivo greenhouse results. This concurrence suggests that these in silico models of C1 metabolism
may provide a viable and validated platform for biosafety assessment of GMOs, and
aid in selecting rational criteria for informing in vitro and in vivo efforts to more accurately decide in the problem formulation phase whose parameters
need to be assessed so that conclusion on “substantial equivalence” or material
difference of a GMO and its non-GMO counterpart can be drawn on a well-grounded
basis.