Genetically modified microorganisms that have the ability to convert carbon substrates into chemical products such as isobutanol are disclosed. For example, genetically modified methanotrophs that are capable of generating isobutanol at high titers from a methane source are disclosed. Methods of making these genetically modified microorganisms and methods of using them are also disclosed.

Related are a recombinant microorganism for producing L-valine, a construction method and an application thereof. Through transferring an amino acid dehydrogenase gene and/or activating activity of a transhydrogenase and/or a NAD kinase, reducing power of NADPH in cell is increased, the titer and yield of L-valine generated by Escherichia coli are improved, and the production of L-valine by one-step anaerobic fermentation is achieved.

The biological production of beta-hydroxyisovalerate (βHIV) using a non-natural microorganism. The non-natural microorganism for the biologically-derived βHIV provides more beta-hydroxyisovalerate synthase activity than the wild-type parent. The non-natural microorganism can host a non-natural enzyme, such as the non-natural enzyme expressed in a yeast or bacteria, wherein the non-natural microorganism comprises an active βHIV metabolic pathway for the production of βHIV. The biological derivation of βHIV eliminates toxic by-products and impurities that result from the chemical production of βHIV, such that βHIV produced by a non-natural microorganism prior to any isolation or purification process has not been in substantial contact with any halogen-containing component.

Methods and materials related to producing isobutyric acid are disclosed. Specifically, isolated nucleic acids, polypeptides, host cells, methods and materials for producing isobutyric by direct microbial fermentation from a carbon source are disclosed.

The present invention relates to a process of producing isobutanol, including: mixing water, lactate, an enzyme mixture including at least one enzyme, at least one cofactor, and at least one coenzyme, to prepare a reaction mixture; allowing catalytic conversions of lactate in the reaction mixture for a sufficient amount of time to produce isobutanol; and separating the isobutanol from a reactant obtained by the catalytic conversions, in which the conversion of lactate into isobutanol is in association with a NADH.sup.+/NADH and/or NADP.sup.+/NADPH regenerating system.

The invention relates to recombinant host cells having at least one integrated polynucleotide encoding a polypeptide that catalyzes a step in a pyruvate-utilizing biosynthetic pathway, e.g., pyruvate to acetolactate conversion. The invention also relates to methods of increasing the biosynthetic production of isobutanol, 2,3-butanediol, 2-butanol or 2-butanone using such host cells.

Multi-carbon compounds such as ethanol, n-butanol, sec-butanol, isobutanol, tert-butanol, fatty (or aliphatic long chain) alcohols, fatty acid methyl esters, 2,3-butanediol and the like, are important industrial commodity chemicals with a variety of applications. The present invention provides metabolically engineered host microorganisms which metabolize methane (CH.sub.4) as their sole carbon source to produce multi-carbon compounds for use in fuels (e.g., bio-fuel, bio-diesel) and bio-based chemicals. Furthermore, use of the metabolically engineered host microorganisms of the invention (which utilize methane as the sole carbon source) mitigate current industry practices and methods of producing multi-carbon compounds from petroleum or petroleum-derived feedstocks, and ameliorate much of the ongoing depletion of arable food source “farmland” currently being diverted to grow bio-fuel feedstocks, and as such, improve the environmental footprint of future bio-fuel, bio-diesel and bio-based chemical compositions.

The biological production of beta-hydroxyisovalerate (βHIV) using at least one non-natural enzyme. The non-natural enzyme for the biologically-derived βHIV provides more beta-hydroxyisovalerate synthase activity than the wild-type parent. The non-natural enzyme having one or more modifications of substrate-specificity positions. The non-natural enzyme can be expressed in a microorganism, such as a yeast or bacteria, wherein the microorganism comprises an active βHIV metabolic pathway for the production of βHIV. Alternatively, the non-natural enzyme can be a βHIV synthase used to produce βHIV in a cell-free environment. The biological derivation of βHIV eliminates toxic by-products and impurities that result from the chemical production of βHIV, such that βHIV produced by a non-natural enzyme prior to any isolation or purification process has not been in substantial contact with any halogen-containing component.

Genetically modified microorganisms that have the ability to convert carbon substrates into multicarbon products. Methods of making these genetically modified microorganisms and methods of using them. Vectors encoding enzymes for use in converting carbon substrates into multicarbon products.

The present invention relates to preparation of key drug intermediate, L-2-amino butyric acid (L-2-ABA) by a method of cell free system and biotransformation using genetically engineered strains from easily available economic substrates like citramalate or citraconate and enzymes like LeuCD, LeuB and ValDH or IlvE.