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Updated: Jun 17, 2026

A Customizable Approach for the Enzymatic Production and Purification of Diterpenoid Natural Products
Published on: October 4, 2019
Investigating Terpene Synthase-Catalyzed Reactions with Ketone- and Alkene-Modified Substrate Analogs
Ruilong Li1,2,3, Minghui Xie1,4, Rongxiang Yin1,5
1Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.
Abstract:
Terpene synthases (TPSs) exhibit remarkable catalytic plasticity, yet their ability to process heteroatom-modified substrates remains poorly understood. Here, three ketone-containing farnesyl pyrophosphate (FPP) analogs were designed and synthesized to probe the influence of carbonyl incorporation on TPS-catalyzed reactions, with structurally related alkene analogs as controls. Six mechanistically distinct sesquiterpene synthases were evaluated for substrate acceptance and product outcomes. Ketone substitution induced pronounced, position-dependent effects, often suppressing canonical cyclization pathways, whereas alkene-modified substrates were more broadly tolerated and generated diverse cyclized products. Across all enzyme-substrate combinations, more than 20 previously unreported terpenoid compounds were obtained and structurally characterized. Several products displayed potent antiproliferative activity against human cancer cell lines, with low cytotoxicity toward normal cells, highlighting the potential of substrate engineering combined with TPS catalysis to expand terpenoid chemical space and access new bioactive compounds.
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