Towards programming-based synthetic genetic circuit enabled high-lysine maize

Abstract

Although a major grain crop, maize is a deficit in Lysine (Lys), which is one of the essential amino acids (EAAs). Several attempts of molecular biology, conventional breeding, marker-assisted breeding, and single/multiple transgenesis have significantly increased Lys content in maize seed. However, till now, no commercial high-Lys maize for human consumption is available in the global market. Therefore, alternative strategies are needed that be adopted over the above-mentioned techniques to develop high-Lys maize. In addition to microbes, circuit-enabled programming-based synthetic biology has significantly improved the desired characteristics of crops including maize as synthetic mini chromosomes have already been built and transferred into maize. The above technology is advantageous as it is a precisely guided artificially controlled system that acts better in addition to the natural system or over the natural system. During the designing and programming of the synthetic genetic circuit for high-Lys maize, a deep understanding of natural Lys biosynthesis pathways, Lys metabolism, metabolic flux, metabolic interconnections, transporters, and transcription factor, post-translational protein regulation are needed. Hence, major genes in aspartate (Asp) pathway, like dihydrodipicolinate synthase (DHPS), aspartate kinase (AK), Lys-ketoglutarate reductase/saccharopine dehydrogenase (LKR/SDH) should be critically analyzed in maize before incorporating these into high-Lys synthetic genetic circuit. Indeed, a prototype of the synthetic high-Lys genetic circuits must have a synthetic switch for precise regulation of multiplex gene expression, memory circuits, synthetic boolean logic gates, and synthetic intercellular communication systems. For proper transformation of the synthetic high-Lys genetic circuit, the landing pad should be specific. Then, precise monitoring and remote regulation of the circuit over several generations might be done to obtain stable programmed high-Lys synthetic maize. Therefore, considering the current advancement of single/multiple transgenesis, conventional breeding, marker-assisted breeding that successfully increased maize Lys, precise programming-based synthetic genetic circuits should be designed for getting high-Lys maize following the mechanism of how the synthetic genetic circuits would work in the maize genome and its remote control. These need deep understanding in maize biology, integration of previously published transgenesis for high-Lys maize, in silico, in vitro and in vivo experiments for successful development of programming-based synthetic genetic circuit enabled high-Lys maize.