Citric acid microbial synthesis

There are many organic acids that can be produced by microbial or biochemical means. However, at present, only acetic acid (as vinegar), citric acid, itaconic acid, gluconic acid, 2-keto-gulonic acid, and lactic acid are produced industrially by fermentation. Other organic acids, such as fumaric, gallic, malic, and tartaric acids, once produced by fermentation or enzyme processes, are now produced commercially, predominantly by the more economic means of chemical synthesis. 

Synthesis of a suitable substrate from citric acid 51 was straightforward17 and Ohno18 found that the Cbz-protected dimethyl ester 53 could be desymmetrised efficiently with pig liver esterase (PLE) or with even higher enantioselectivity, with the microbial enzyme from Flavobacterium lutescens (98% ee). The P-lactam 48 could be closed by the dipyridine-disulfide/Ph3P method. 

O-Ketoglutaric Acid. 2-Oxopentanedioic acid 2-oxoglutaric acid 2-oxo-l,5-pentanedioic acid. CsH40 mol wt 146.10. C 41.10%, H 4.14%, O 54.76%. HOOC. CH.CHjCOCOOH. Plays an important role in amino add metabolism (transamination) see Severo Ochoa, "Enzymic Mechanisms in the Citric Acid Cycle in Advances fn Enzy-mology 15, 183-270 (1954). Prepn Friedman, Kosower, Org. Syn. cell. vol. Ill, 510 (1955) Bottorff. Moore, ibid. Coll. vol. V, 687 (1973). Microbial synthesis using a strain of Pseudomonas Lockwood et al. U.S. pat. 2,443,919 (1948) Berger, Witt, U.S. pat. 2,841,616 (1958). 

Occasionally the synthesis of a microbial product, for example that of ethanol from glucose, is catalysed by non-viable cells (section 6.2.1.1). Then the process is properly catalytic because the Saccharomyces cerevisiae cells do not change, for a time at least. However there are some industrially important reactions in which micro-organisms are first grown to a high biomass and are then added to a substrate which is almost quantitatively converted to a product. These are effectively catalytic processes in which one or a few enzymes in the organism transform an added substrate into a useful product. These transformations are divorced from cell growth, in contrast to syntheses such as those in which carbohydrates are converted into citric acid or complex feedstocks into secondary metabolites. 

The results are of comparative interest but may have little bearing on the present discussion because the regulatory mechanisms for microbial fatty acid synthesis and for fatty acid synthesis in animal tissues appear to operate at quite different sites of control. Apart from the obvious absence of primary hormonal signals in bacteria, the following differences stand out. Only animal tissue acetyl-CoA carboxylase is activated by citric acid bacterial, plant and yeast carboxylase do not respond to this type of allosteric modulation. Similarly, microbial acetyl-CoA carboxylases are much more resistant to inhibition by palmitoyl-CoA at least at the concentration which inhibit the hepatic enzyme. 

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