4.7 Review

Metabolic engineering of Yarrowia lipolytica for terpenoids production: advances and perspectives

Journal

CRITICAL REVIEWS IN BIOTECHNOLOGY
Volume 42, Issue 4, Pages 618-633

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1080/07388551.2021.1947183

Keywords

Yarrowia lipolytica; terpenoid; terpene synthase; metabolic engineering; fine-tuning; mevalonate pathway; microbial production

Funding

  1. Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project [TSBICIP-CXRC-002, TSBICIP-IJCP-002]
  2. Hundreds of Talents Program of the Chinese Academy of Sciences [Y0J51009]
  3. National Natural Science Foundation of China [32071423]

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Terpenoids are a diverse family of natural products widely used in various fields, but traditional production methods are inefficient. Microbial cell factories, particularly Yarrowia lipolytica, offer a sustainable alternative for terpenoid production. Through metabolic engineering strategies, Y. lipolytica can serve as an efficient biomanufacturing factory for terpenoids.
Terpenoids are a large family of natural products with diversified structures and functions that are widely used in the food, pharmaceutical, cosmetic, and agricultural fields. However, the traditional methods of terpenoids production such as plant extraction and chemical synthesis are inefficient due to the complex processes, high energy consumption, and low yields. With progress in metabolic engineering and synthetic biology, microbial cell factories provide an interesting alternative for the sustainable production of terpenoids. The non-conventional yeast, Yarrowia lipolytica, is a promising host for terpenoid biosynthesis due to its inherent mevalonate pathway, high fluxes of acetyl-CoA and NADPH, and the naturally hydrophobic microenvironment. In this review, we highlight progress in the engineering of Y. lipolytica as terpenoid biomanufacturing factories, describing the different terpenoid biosynthetic pathways and summarizing various metabolic engineering strategies, including progress in genetic manipulation, dynamic regulation, organelle engineering, and terpene synthase variants.

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