Biosynthesis of Trehangelin in Polymorphospora rubra K07–0510: Identification of Metabolic Pathway to Angelyl‐CoA |
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Authors: | Dr. Yuki Inahashi Taro Shiraishi Dr. Kaia Palm Prof. Dr. Yoko Takahashi Prof. Dr. Satoshi Ōmura Prof. Dr. Tomohisa Kuzuyama Dr. Takuji Nakashima |
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Affiliation: | 1. Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan;2. Laboratory of Cell Biotechnology, Biotechnology Research Center, The University of Tokyo, Tokyo, Japan;3. Protobios Llc, Tallinn, Estonia |
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Abstract: | Trehangelins are trehalose angelates discovered from endophytic actinomycete Polymorphospora rubra K07‐0510. We identified the trehangelin biosynthetic gene cluster, including genes that encode a glycoside hydrolase‐like protein (thgC), α‐amylase (thgD), 3‐ketoacyl‐ACP synthase III (thgI), 3‐ketoacyl‐ACP reductase (thgK), enoyl‐CoA hydratase (thgH) and acyl transferase (thgJ). Heterologous expression of thgH, thgI, thgJ and thgK confirmed the importance of these genes in the biosynthesis of trehangelin A. Enzymatic activity studies showed that ThgI catalyses the condensation of acetyl‐CoA and methylmalonyl‐CoA to 2‐methylacetoacetyl‐CoA (MAA‐CoA), ThgK catalyses NADPH‐dependent reduction of MAA‐CoA to 3‐hydroxy‐2‐methylbutyryl‐CoA (HMB‐CoA) and ThgH catalyses the dehydration of HMB‐CoA to angelyl‐CoA (AN‐CoA). This is the first report on the elucidation of the enzymatic formation of AN‐CoA. |
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Keywords: | angelate angelyl-CoA biosynthesis endophytic actinomycete natural products trehangelin |
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