Betaine Enhancement of Fermentation to make C4 Diacids

Abstract

A method of making a C4 diacid from a sugar source by fermentation with a microorganism is described that includes supplementing the fermentation medium with relatively low amounts of betaine. The use of betaine can substantially reduce or even completely eliminate the need for complex nutrient source such as yeast extract, and eliminate a need for vitamins such as biotin, while maintaining a high level of production of the C4 diacid from a simplified sugar based media. The use of betaine improves yield from sugar, final titer, and rate of production per hour. The method is particularly suitable for microorganisms that otherwise display a dependence on yeast extract for high productivity, more particularly for any bacteria, and most particularly for the production of succinic acid from the bacterium Actinobacillus succinogenes. An improved strain of A succinogenes is also described, having a mutation in a betaine transporter that improves C4 diacid production in the presence of betaine.

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