3‐Hydroxypropionate production from <i>myo</i> ‐inositol by the gut acetogen <i>Blautia schinkii</i>

Species of the genus Blautia are not only abundant in the human gut but also contribute to human well-being. Our study demonstrates that the gut acetogen Blautia schinkii can grow on myo-inositol. We identified the pathway of myo-inositol degradation through a combination of physiological and biochemical studies, genome-wide expression profiling and homology searches. Initially, myo-inositol is oxidized to 2-keto-myo-inositol. This compound is then metabolized by a series of enzymes - a dehydratase, hydrolase, isomerase and kinase - to form 2-deoxy-5-keto-d-gluconic acid 6-phosphate. This intermediate is split by an aldolase into malonate semialdehyde and dihydroxyacetone phosphate, which is an intermediate of the Embden-Meyerhof-Parnas pathway. This pathway leads to the production of pyruvate and, subsequently, acetate. Concurrently, malonate semialdehyde is reduced to 3-hydroxypropionate (3-HP). The genes responsible for myo-inositol degradation are clustered on the genome, except for the gene encoding the aldolase. We identified the putative aldolase Fba_3 and 3-HP dehydrogenase Adh1 encoding genes bioinformatically and verified them biochemically using enzyme assays with heterologously produced and purified protein. The major fermentation end products were 3-HP and acetate, produced in similar amounts. The production of the unusual fermentation end product 3-HP is significant not only for human health but also for the potential bioindustrial production of this highly desired compound.