The present disclosure provides microbial organisms having decreased production of unwanted by-products (e.g, pyruvate-, CO.sub.2—, TCA-derived by-products; acetate; ethanol; and/or, alanine) to enhance carbon flux through acetyl-CoA, which can increase production of acetyl-CoA derived compounds (e.g, 1,3-BDO, MMA, and (3R)-hydroxybutyl (3R)-hydroxybutyrate, or any other acetyl-CoA derived compounds), and products made from any of these compounds. Also provided are one or more exogenous nucleic acids encoding enzymes that can decrease production of unwanted by-products (e.g, aldehyde dehydrogenase, acetyl-CoA synthase, amino acid dehydrogenase, alanine racemase, and/or citrate synthase), and/or one or more gene attenuations occurring in genes (e.g., acetolactate synthase) that result in decreased production of unwanted by-products. Various combinations of the exogenous nucleic acids and gene deletions are also provided in the present disclosure. Methods of making and using the same, including methods for culturing cells, and for the production of the various products are also provided.