Inspired by the exponential growth of the microelectronic industry, my lab has been attempting to build a biofoundry that integrates biology, automation and artificial intelligence (AI)/machine learning for rapid prototyping and manufacturing of biological systems for synthesis of bioproducts ranging from chemicals to materials to therapeutic agents. In this talk, I will discuss the challenges and opportunities at the nexus of synthetic biology, machine learning, and automation and highlight a few of our accomplishments and the recently launched NSF AI research institute for molecular synthesis. Specifically, I will introduce three interconnected stories, including: (1) development of the Illinois Biological Foundry for Advanced Biomanufacturing (iBioFAB) for next-generation synthetic biology applications; (2) development of genome-scale engineering tools for rapid metabolic engineering applications, and (3) integration of biocatalysis and chemical catalysis for synthesis of value-added chemicals, which necessitates the development of AI-enabled synthesis planning and catalyst design tools.