Amyris, Inc.

Total Marketing Services

Annie Ening Tsong

Adam Meadows

Kristy Michelle Hawkins

Yoseph Tsegaye

Timothy Stevens Gardner

Hanxiao Jiang

Penelope R Chua

Tina Tipawan Mahatdejkul-Meadows

Joshua Adam Lerman

Lauren Barbara Pickens

Anna Tai

Chandresh Thakker

Thomas Jon Scherbart

Adam Leon Meadows

Provided herein are compositions and methods for uncoupling the yield and productivity of an isoprenoid compound produced in a host cell. In some embodiments, the yield and productivity are uncoupled by genetically modifying the host cell to reduce flux through the citric acid cycle (TCA). In other embodiments, the yield and productivity are uncoupled by reducing the levels of ATP in the host cell.

Methods for decoupling yield and productivity of a non-catabolic compound produced by a host cell

Provided herein are compositions and methods for the heterologous production of acetyl-CoA-derived isoprenoids in a host cell. In some embodiments, the host cell is genetically modified to comprise a heterologous nucleotide sequence encoding an acetaldehyde dehydrogenase, acetylating (ADA, E.C. 1.2.1.10) and an MEV pathway comprising an NADH-using HMG-CoA reductase. In some embodiments, the host cell is genetically modified to comprise a heterologous nucleotide sequence encoding an ADA and an MEV pathway comprising an acetoacetyl-CoA synthase. In some embodiments, the genetically modified host cell further comprises one or more heterologous nucleotide sequences encoding a phosphoketolase and a phosphotransacetylase. In some embodiments, the genetically modified host cell further comprises a functional disruption of the native PDH-bypass. The compositions and methods described herein provide an energy-efficient yet redox balanced route for the heterologous production of acetyl-CoA-derived isoprenoids.

Production of acetyl-coenzyme a derived isoprenoids

Provided herein are compositions and methods for improved production of acetyl-CoA and acetyl-CoA derived compounds in a host cell. In some embodiments, the host cell is genetically modified to comprise a heterologous nucleotide sequence encoding a phosphoketolase (PK), and a functional disruption of an endogenous enzyme that converts acetyl phosphate to acetate. In some embodiments, the host cell further comprises a heterologous nucleotide sequence encoding a phosphotransacetylase (PTA). In some embodiments, the enzyme that converts acetyl phosphate to acetate is a glycerol-1-phosphatase. In some embodiments, the glycerol-1-phosphatase is GPP1/RHR2. In some embodiments, the glycerol-1-phosphatase is GPP2/HOR2. The compositions and methods described herein provide an efficient route for the heterologous production of acetyl-CoA-derived compounds, including but not limited to, isoprenoids, polyketides, and fatty acids.

Use of phosphoketolase and phosphotransacetylase for production of acetyl-coenzyme A derived compounds

Production of acetyl-coenzyme A derived isoprenoids

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Emeryville, CA, United States of America

Annie Ening Tsong