| Summary: | Abstract It is an increasingly promising research direction using microbiomes to produce various chemicals in order to support people's growing need for sustainability. Currently, bottom‐up constructed defined microbiomes and top‐down constructed undefined microbiomes play an essential role in the fields of synthetic biology and environmental engineering, respectively. However, if we are goal‐oriented and want to align scientific principles with technology and engineering in future waste biorefinery, we need to reconsider and design microbiomes interdisciplinarily. In this editorial, we briefly review the latest applications of two approaches to microbiome design (bottom‐up and top‐down) and the dilemmas faced in using complex waste. Consequently, we introduce the concept of ‘sustainable synthetic microbiomics’ to apply combined bottom‐up and top‐down constructed microbiomes to provide products for human needs from low‐value waste. Furthermore, we outline the relatively comprehensive research contents and expected prospects based on the pressing problems. Finally, burning questions on key research contents are proposed for specific cases, hoping to provide valuable views for future microbiome biorefinery.
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