Designer Microbial Ecosystems - Toward Biosynthesis with Engineered Microbial Consortia

Beyond characterizing the complex pathways of natural product synthesis in native organisms, the ability to engineer these pathways into different microbial hosts amenable to optimized bioprocessing is critical to increase the availability of natural products that are difficult to synthesize or currently realized in low yields. The field of synthetic biology has greatly advanced our ability to heterologously express genes in non-native hosts, and has improvedour capability to produce desirable natural products. However, complex biochemical synthesis, even among the most robust and genetically tractable microorganisms, can place a large metabolic burden on the engineered cell and poses significant engineering challenges. A new approach to enhance natural product synthesis could exploit the metabolic diversity of multiple engineered cells with each celltype carryingout a portion of the overall pathway. Dividing the work of synthesizing complex chemical structures among multiple organisms could allow bioprocesses to be better optimized for specific natural product synthesis. This chapter will discuss how such cooperative multicellular systems capable of complex biosynthesis could be established through the implementation of suitable population control systems that involve cell-to-cell communication circuits designed from microbial quorum sensing systems. The discussion will focus on the trade-offs and implications for large-scale process design, optimization and control of bioreactors. The challenge of establishing and maintaining robust processes for biosynthesis will require new molecular and microbial tools to be devised. Of these new toolsets to be established, engineered synthetic consortia, which maintaincooperative synthesis, will be essential for effective bioprocess designs in the future.