Genomatica, Inc.

Tae Hoon Yang

Anthony P Burgard

Priti Pharkya

Robin E Osterhout

Stephen J Van Dien

Jungik Choi

Harish Nagarajan

Ali Khodayari

The invention is directed to a non-naturally occurring microbial organism comprising a first attenuation of a succinyl-CoA synthetase or transferase and at least a second attenuation of a succinyl-CoA converting enzyme or a gene encoding a succinate producing enzyme within a multi-step pathway having a net conversion of succinyl-CoA to succinate.

Methods and organisms with increased carbon flux efficiencies

Described herein are engineered cells including ones having synthetic methylotrophy which include an NADH-dependent enzyme capable of converting G3P to 3PG (e.g.,gapN) and/or fructose-1,6-bisphosphatase, along with hexulose-6-phosphate synthase, 6-phospho-3-hexuloisomerase, a phosphoketolase, or a combination thereof. Engineered cells of the disclosure beneficially maintain adequate pool sizes of phosphorylated C3 and/or C4 compounds, and/or provide increased levels of NADPH. As such, the modifications allow for the generation of C6 compounds from C1 (e.g., a methanol feedstod) and C5 compounds, the regeneration of C5 compounds from C6 compounds by carbon rearrangement, and an improved balance between regeneration of C5 compounds and lower glycolysis. In turn, this allows the engineered microorganism to generate sufficient quantities of metabolic precursors (e.g., acetyl-CoA) which can be used in a bioproduct pathway, and the engineered cells can include further modifications to those pathway enzymes allowing for production of a desired bioproduct.

Engineered microorganisms with G3P → 3PG enzyme and/or fructose-1,6-bisphosphatase including those having synthetic or enhanced methylotrophy

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San Diego, CA, United States of America

Tae Hoon Yang