Production of compounds derived from acetyl-coenzyme A

Abstract

The present disclosure relates to the use of pantothenate compounds as a non-genetic switch for the production of heterologous acetyl-CoA derived (HACD) compounds in microbial host cells. The invention provides genetically modified microorganisms that are more stable when stored and initially cultured under reduced pantothenate concentrations, cell culture media having reduced concentrations of pantothenate compounds, and methods of producing HACD compounds using the cell culture media and the genetically engineered microorganisms of the invention.

Description

[0001] 1. Cross references to related applications [0002] This application claims priority to US Provisional Patent Application No. 61 / 483,896, filed May 9, 2011, which is incorporated herein by reference. 2. Technical fields [0003] The present disclosure relates to the use of pantothenate (also known as vitamin B5) as a non-genetic switch for regulating the production of heterologous acetyl-CoA-derived compounds by genetically modified host cells. 3. Background technology [0004] The advent of synthetic biology has brought forth the promise of using fermentative microorganisms to produce biofuels, chemical reagents, and biomaterials from renewable sources at industrial scale and quality. For example, functional non-native biological pathways have been successfully constructed in microbial hosts for the production of: precursors of the antimalarial drug artemisinin (see, e.g., Martin et al., Nat Biotechnol 21:796-802 (2003 ); fatty acid-derived fuels and chemicals (e.g...

AI Technical Summary

Problems solved by technology

Genetic switches are a common way of achieving this in practice, but may have disadvantages due to, for example, the cost of exogenous inducers, delays in transcription and translation of the switch, and if mutations occur in the genetic switch itself, can also be a source of low productivity

However, metabolic switches do not have these disadvantages

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