Recently, our group developed a host-specific engineering framework for the efficient biosynthesis of sclareol in Pichia pastoris.

Although P. pastoris is widely recognized for recombinant protein production, its tightly regulated metabolism imposes metabolic rigidity that limits the overproduction of small-molecules. By integrating pathway rewiring, regulatory remodeling, and fermentation optimization, the engineered strain achieved a sclareol titer of 27.8 g/L in a 1.5-L bioreactor by using glycerol as the carbon source, representing the highest titer reported to date.

This work expands the utility of P. pastoris as a versatile chassis for natural product biosynthesis and provides a generalizable roadmap for engineering other non-conventional hosts.

This study was recently published in Trends in Biotechnology. The research was supported by the Polish-Chinese Funding Initiative of NSFC and NCN, the CAS-Iranian Vice Presidency for Science and Technology Joint Research Project, the Liaoning Binhai Laboratory Project and the Liaoning Provincial Science and Technology Plan Project (Text and image by Mengyao Zhang).

Link: https://doi.org/10.1016/j.tibtech.2026.04.026

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