Method for controlling biooxidation reactions

Abstract

Biooxidation reactions can be controlled by a method which comprises the steps of: (1) independently adding a substrate and a co-substrate at predetermined rates to a bioxidation reaction mixture comprised of a biocatalyst; (2) measuring the oxygen consumption rate and carbon dioxide evolution rate from the reaction mixture; (3) determining the instantaneous rates of substrate and cosubstrate consumption by solving simultaneous equations relating carbon dioxide evolution rate and oxygen consumption rate to the substrate oxidation stoichiometry, the cosubstrate combustion stoichiometry, and optionally the biomass formation stoichiometry; (4) simultaneously adjusting the substrate and cosubstrate addition rates to the rates of substrate oxidation and cosubstrate consumption in order to maximize the rate of product formation while simultaneously minimizing the rate of cosubstrate usage. The method provides a rapid means of controlling fed-batch biooxidation reactions which can employ in-line techniques and is broadly applicable for diverse oxidation reactions.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of also co-pending Application Serial No. 60 / 439,991, filed January 14, 2003, which is incorporated herein by reference in its entirety. [0003] Statement Regarding Federally Sponsored Research or Development [0004] This invention was made at least in part with funding granted under NIST-ATP Contract No. 70NANB8H4033, Department of Commerce. The government may thus have certain rights in the invention. Background of the invention [0005] Enzymes and microorganisms naturally catalyze a wide range of oxidation reactions by directly reducing molecular oxygen. From a biochemical point of view, these highly irreversible reactions are considered to be very violent, releasing much of the free energy of the reaction in the form of heat. In general, the basic mechanism of biooxidation of many different organic substrates can be regarded as the activation of molecular oxygen to form hi...

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Problems solved by technology

[0013] 5) Expensive; placing a large amount of substrate in the container increases the risk of batch damage due to equipment failure or contamination;

[0015] 7) Problems arise in recovering or purifying the product;

Although products, substrates, and co-substrates can be analyzed offline using various analytical techniques, such methods tend to be cumbersome and of little value for real-time control of nutrient feeding in these fed-batch reactions

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