Geranylgeraniol: Bio-based platform for teprenone, menaquinone-4, and α-tocotrienol synthesis.

By utilizing the conformational selectivity of biosynthesis and the flexibility of chemical synthesis, researchers have formulated metabolic engineering-based semi-synthetic approaches that initiate with the final product's structure and identify key biosynthesis intermediates. Nonetheless, these tailored semi-synthetic routes focused on end-products, neglecting the possibility of biobased intermediates as a platform for derivatization. To address this challenge, this studyproposed a novel strategy resembling chemosynthesis-style divergent exploration to amplify the significance of biobased intermediates, in the case of geranylgeraniol (GGOH). Using the novel bifunctional terpene synthase PTTC066 and systematic metabolic engineering modifications, the engineered yeast straindemonstrated high GGOH production levels (3.32 g/L, 0.039 g/L/h). This platformenabled the semi-synthesis of various pharmaceuticals, including the anti-ulcer drug teprenone, the osteoporosis treatment drug menaquinone-4, and introduced a novel route for synthesizingα-tocotrienol. This study offers a fresh outlook on semi-synthetic approaches, opening avenues for improvements, substitutions, and innovations in industrial production processes.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tiangang, Liu reports financial support was provided by Wuhan Hesheng Technology Co., Ltd. Wuhan University and Wuhan Hesheng Technology Co., Ltd have applied for several patents based on this work. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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