Regulation of acetohydroxy acid synthase in Corynebacterium glutamicum during fermentation of ?-ketobutyrate to l-isoleucine

Eggeling, Iris; Cordes, Christiana; Eggeling, Lothar; Sahm, Hermann

doi:10.1007/bf00252545

Cited by 112 publications

(94 citation statements)

References 17 publications

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“…developed a fermentation process in E. coli for the production of d-pantothenic acid (d-62), whereby high end concentrations were observed upon feeding with b-alanine (74; > 60 g L À1 of d-62 after a fermentation time of 72 h). [89] Researchers at Degussa, in cooperation with the research groups of Pühler and Sahm, are currently working on a method based on this process for the synthesis of pantothenic acid by fermentation in E. coli [90] and Corynebacterium glutamicum, [91] respectively. The genes relevant for pantothenic acid biosynthesis were over-expressed, and the production of the precursor a-ketoisovalerate (75) was increased by ilvBNCD over-expression and ilvA deletion.…”

Section: Enzymatic Hydrolysis Of Nitrilesmentioning

confidence: 99%

Industrial Methods for the Production of Optically Active Intermediates

Breuer¹,

Ditrich²,

Habicher³

et al. 2004

Angew Chem Int Ed

1,334

625

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Enantiomerically pure amino acids, amino alcohols, amines, alcohols, and epoxides play an increasingly important role as intermediates in the pharmaceutical industry and agrochemistry, where both a high degree of purity and large quantities of the compounds are required. The chemical industry has primarily relied upon established chemical methods for the synthesis of these intermediates, but is now turning more and more to enzymatic and biotechnological fermentation processes. For the industrial implementation of many transformations alternative methods are available. The advantages of the individual methods will be discussed herein and exemplified by syntheses of relevant compounds.

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Section: Enzymatic Hydrolysis Of Nitrilesmentioning

confidence: 99%

Industrial Methods for the Production of Optically Active Intermediates

Breuer¹,

Ditrich²,

Habicher³

et al. 2004

Angew Chem Int Ed

1,334

625

View full text Add to dashboard Cite

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“…Furthermore, for these bacteria as for E. coli, LeuA and IlvA were shown to be regulated by retroinhibition in the presence of leucine and isoleucine, respectively (23,38,41,58,60). Lastly, in E. coli and C. glutamicum, IlvBN is inhibited by valine (12).…”

mentioning

confidence: 96%

Dual role of alpha-acetolactate decarboxylase in Lactococcus lactis subsp. lactis

et al. 1997

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The ␣-acetolactate decarboxylase gene aldB is clustered with the genes for the branched-chain amino acids (BCAA) in Lactococcus lactis subsp. lactis. It can be transcribed with BCAA genes under isoleucine regulation or independently of BCAA synthesis under the control of its own promoter. The product of aldB is responsible for leucine sensibility under valine starvation. In the presence of more than 10 M leucine, the ␣-acetolactate produced by the biosynthetic acetohydroxy acid synthase IlvBN is transformed to acetoin by AldB and, consequently, is not available for valine synthesis. AldB is also involved in acetoin formation in the 2,3-butanediol pathway, initiated by the catabolic acetolactate synthase, AlsS. The differences in the genetic organization, the expression, and the kinetics parameters of these enzymes between L. lactis and Klebsiella terrigena, Bacillus subtilis, or Leuconostoc oenos suggest that this pathway plays a different role in the metabolism in these bacteria. Thus, the ␣-acetolactate decarboxylase from L. lactis plays a dual role in the cell: (i) as key regulator of valine and leucine biosynthesis, by controlling the acetolactate flux by a shift to catabolism; and (ii) as an enzyme catalyzing the second step of the 2,3-butanediol pathway.Synthesis of the three branched-chain amino acids (BCAA), leucine, isoleucine, and valine, has been studied in detail in organisms as diverse as bacteria, fungi, and plants (for reviews, see references 8, 32, 57, and 58). A particular feature of this synthesis is that it is carried out, in part, by the same enzymes for the three amino acids (Fig. 1). However, the relative amounts of the three amino acids in cell proteins are not the same, since leucine, valine, and isoleucine represent 39, 36, and 25%, respectively, of the total BCAA in Escherichia coli (40). Regulation of the BCAA synthesis is therefore necessarily complex. A global regulation model has been established only for E. coli (58). Two levels of regulation, concerning gene transcription and enzyme inhibition, have previously been described.E. coli genes which encode BCAA synthesis enzymes form three clusters and are organized in five transcription units (2). Initiation of transcription of all the genes except ilvC is regulated by nonspecific, pleiotropic regulators responding to amino acid starvation and different changes in the medium (58). In addition to this control, a mechanism of transcriptional attenuation dependent on the synthesis of a leader peptide as described first for the tryptophan operon (33) negatively regulates ilvBN, ilvGMEDA, and leuABCD. These mechanisms allow the expression of the enzymes necessary for BCAA synthesis when needed.Activity of several BCAA-synthesizing enzymes is regulated by retroinhibition (Fig. 1). This control is simple in the case of leucine and isoleucine, since each amino acid inhibits an enzyme specific for an early step of its synthesis (LeuA and IlvA, respectively [53,57]). In contrast, the first enzyme involved in valine synthesis is also required fo...

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“…Another relevant target is the dapA gene, encoding dihydrodipicolinate synthase. Amplified expression, increasing lysine was realized using plasmids [138, [142][143][144] as well as mutation of the promoter sequence [145]. Also, overproduction of diaminopimelate epimerase (DapF) and succinyl-aminoketopimelate transaminase (DapC), two enzymes of the succinylase branch, was beneficial for lysine formation [137].…”

Section: Metabolic Engineering Of Lysine Biosynthesismentioning

confidence: 99%

Analysis and Engineering of Metabolic Pathway Fluxes in Corynebacterium glutamicum

Wittmann

2010

Biosystems Engineering I

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The Gram-positive soil bacterium Corynebacterium glutamicum was discovered as a natural overproducer of glutamate about 50 years ago. Linked to the steadily increasing economical importance of this microorganism for production of glutamate and other amino acids, the quest for efficient production strains has been an intense area of research during the past few decades. Efficient production strains were created by applying classical mutagenesis and selection and especially metabolic engineering strategies with the advent of recombinant DNA technology. Hereby experimental and computational approaches have provided fascinating insights into the metabolism of this microorganism and directed strain engineering. Today, C. glutamicum is applied to the industrial production of more than 2 million tons of amino acids per year. The huge achievements in recent years, including the sequencing of the complete genome and efficient post genomic approaches, now provide the basis for a new, fascinating era of research -analysis of metabolic and regulatory properties of C. glutamicum on a global scale towards novel and superior bioprocesses.

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Regulation of acetohydroxy acid synthase in Corynebacterium glutamicum during fermentation of ?-ketobutyrate to l-isoleucine

Cited by 112 publications

References 17 publications

Industrial Methods for the Production of Optically Active Intermediates

Industrial Methods for the Production of Optically Active Intermediates

Dual role of alpha-acetolactate decarboxylase in Lactococcus lactis subsp. lactis

Analysis and Engineering of Metabolic Pathway Fluxes in Corynebacterium glutamicum

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