Configurable Full Subtractor and Adder by Lego-like Mixing and Matching of Engineered Bacteria

One of the long-term goals of synthetic bioengineering is to create configurable and programmable biological systems by just mixing and matching "LEGO"-like bio-modules. Here, we introduce a configurable and modular multi-cellular system where, from a small library of nine discrete engineered bacterial cells, a full subtractor and a full adder can be built on demand by just mixing and matching seven appropriate cell types in a culture. Here, each set of engineered bacteria was modelled as an artificial neuro-synapse that, in a co-culture, formed a single layer artificial neural network (ANN) type architecture that worked as a biochemical full subtractor or full adder. The system is configurable with interchangeable cellular modules, whereby through simply interchanging two cell types in the subtractor culture, a full adder can be built and vice versa. This Lego-like mix and match system is mathematically predictive, and provide a flexible and scalable means to build complex cellular functions. This work may have significance in biocomputer technology development, multi-cellular synthetic biology, and cellular hardware for ANN.