Terpenoids have tremendous biological activities and are widely employed in food,healthcare and pharmaceutical industries.Using synthetic biology to product terpenoids from microbial cell factories presents a promisin...Terpenoids have tremendous biological activities and are widely employed in food,healthcare and pharmaceutical industries.Using synthetic biology to product terpenoids from microbial cell factories presents a promising alternative route compared to conventional methods such as chemical synthesis or phytoextraction.The red yeast Rhodotorula mucilaginosa has been widely studied due to its natural production capacity of carotenoid and lipids,indicating a strong endogenous isoprene pathway with readily available metabolic intermediates.This study constructed several engineered strains of R.mucilaginosa with the aim of producing different terpenoids.Monoterpeneα-terpineol was produced by expressing theα-terpineol synthase from Vitis vinifera.The titer ofα-terpineol was further enhanced to 0.39 mg/L by overexpressing the endogenous rate-limiting gene of the MVA pathway.Overexpression ofα-farnesene synthase from Malus domestica,in combination with MVA pathway rate-limiting gene resulted in significant increase inα-farnesene production,reaching a titer of 822 mg/L.The carotenoid degradation productβ-ionone was produced at a titer of 0.87 mg/L by expressing theβ-ionone synthase from Petunia hybrida.This study demonstrates the potential of R.mucilaginosa as a platform host for the direct biosynthesis of various terpenoids and provides insights for further development of such platforms.展开更多
基金National Key Research and Development Program of China(2021YFA0910600)National Natural Science Foundation of China(22308350,22238010)+1 种基金Liaoning Revitalization Talents Program(XLYC2002089)Science and Technology Bureau of Dalian City(2021RT04).
文摘Terpenoids have tremendous biological activities and are widely employed in food,healthcare and pharmaceutical industries.Using synthetic biology to product terpenoids from microbial cell factories presents a promising alternative route compared to conventional methods such as chemical synthesis or phytoextraction.The red yeast Rhodotorula mucilaginosa has been widely studied due to its natural production capacity of carotenoid and lipids,indicating a strong endogenous isoprene pathway with readily available metabolic intermediates.This study constructed several engineered strains of R.mucilaginosa with the aim of producing different terpenoids.Monoterpeneα-terpineol was produced by expressing theα-terpineol synthase from Vitis vinifera.The titer ofα-terpineol was further enhanced to 0.39 mg/L by overexpressing the endogenous rate-limiting gene of the MVA pathway.Overexpression ofα-farnesene synthase from Malus domestica,in combination with MVA pathway rate-limiting gene resulted in significant increase inα-farnesene production,reaching a titer of 822 mg/L.The carotenoid degradation productβ-ionone was produced at a titer of 0.87 mg/L by expressing theβ-ionone synthase from Petunia hybrida.This study demonstrates the potential of R.mucilaginosa as a platform host for the direct biosynthesis of various terpenoids and provides insights for further development of such platforms.