Methanol dehydrogenase fusion proteins

Abstract

Described herein are fusion proteins including methanol dehydrogenase (MeDH) and at least one other polypeptide such as 3-hexulose-6-phosphate dehydrogenase (HPS) or 6-phospho-3-hexuloisomerase (PHI),such as DHAS synthase or fructose-6-Phosphate aldolase or such as DHA synthase or DHA kinase. In a localized manner, the fusion protein can promote the conversion of methanol to formaldehyde and thento a ketose phosphate such as hexulose 6-phosphate or then to DHA and G3P. When expressed in cells, the fusion proteins can promote methanol uptake and rapid conversion to the ketose phosphate or tothe DHA and D3P, which in turn can be used in a pathway for the production of a desired bioproduct. Beneficially, the rapid conversion to the ketose phosphate or to the DHA and G3P can avoid the undesirable accumulation of formaldehyde in the cell. Also described are engineered cells expressing the fusion protein, optionally include one or more additional metabolic pathway transgene(s), methanol metabolic pathway genes, target product pathway genes, cell culture compositions including the cells, methods for promoting production of the target product or intermediate thereof from the cells, compositions including the target product or intermediate, and products made from the target product or intermediate.

Description

[0001] priority claim [0002] This application claims priority to US Provisional Patent Application 62 / 249,032, filed October 30, 2015, and US Provisional Patent Application 62 / 260,189, filed November 25, 2015, the entire contents of which are incorporated herein by reference. At the same time, the entire content of the 28kb ASCII text application titled "GNO0027WO_Sequence_Listing.txt" created on October 26, 2016 is also incorporated into this application by reference. technical field [0003] This application relates to fusion proteins containing methanol dehydrogenase and engineered cells expressing these fusions and methods of using methanol to produce biological products. Background technique [0004] In intracellular metabolic pathways, metabolic intermediates are precursor molecules to pathway products, which are often biologically important molecules. [0005] Various factors can affect the processing of metabolic intermediates in product pathways. Intermediates ...

AI Technical Summary

Problems solved by technology

In other cases, accumulation of metabolic intermediates may have direct adverse effects on cells

For example, elevated concentrations of small molecules such as methylglyoxal or formaldehyde can non-specifically modify intracellular proteins and adversely affect cellular health

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