Biomanufacturing uses the functions of organisms to process and synthesize chemicals on a large scale.Compared to traditional approaches,biomanufacturing method is considered as a green and sustainable one because it normally consumes less energy,generates less wastes yet outputs higher added-value products.It is routine to design and construct microbial cell factories for biomanufacturing applications.However,microbial cell factories often fail to exhibit expected functions due to intrinsic crosstalk mediated by cofactors.This article briefly introduces conventional methods for regulating intracellular redox coenzyme levels and their limitations,highlights the necessity of creating non-natural coenzyme-mediated systems.Furthermore,with nicotinamide cytosine dinucleotide(NCD)and nicotinamide mononucleotide(NMN)as examples,we will discuss how to explore new biological components and redox modules to design new microbial cell factories.Finally,we predict the future directions and analysis the challenges of biomanufacturing based on non-natural cofactors.
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