Natural products - organic compounds synthesized by living organisms - are of immense interest for applications ranging from anticancer drugs to pigments and from flavoring components to antibiotics. These compounds can be difficult to produce using conventional synthetic chemistry, but biological systems can be engineered to synthesize natural products in a more efficient and sustainable manner. iScience and Trends in Biotechnology are excited to collaborate on a special issue containing original research and timely reviews on metabolic engineering for natural products biosynthesis. Wenjun Zhang (WZ) from UC Berkeley (USA) and Sang Yup Lee (SYL) from KAIST (Korea Advanced Institute of Science and Technology), who contributed as guest editors for this joint special issue, discuss the promise of natural products metabolic engineering and explain its potential to create an emerging interdisciplinary community.