Continuous cell-recycle process for l-carnitine production: performance, engineering and downstream processing aspects compared with discontinuous processes

Hoeks, Frans W. J. M. M.; Kulla, Hans G.; Meyer, Hans‐Peter

doi:10.1016/0168-1656(92)90136-w

Cited by 23 publications

(9 citation statements)

References 5 publications

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“…Using the ®rst method, Lonza commercially produces L L-carnitine from c-butyrobetaine as a starting material. Volumetric productivity of the continuous process with recycling is 5.4 g/l/h [50]. To obtain a high yield (greater than 95%), they developed a mutant strain HK 1349, which lacks of carnitine dehydrogenase since L L-carnitine is further degraded into 3-dehydrocarnitine.…”

Section: Discussionmentioning

confidence: 99%

“…However, Lonza concluded that the fed-batch process was more cost effective because it was more inexpensive to purify L L-carnitine. In continuous process 5±10% of c-butyrobetaine remains in the product stream; in the fed batch process, however, more than 99% of c-butyrobetaine has already been converted into L L-carnitine [50]. Since only a few reports are available on L L-carnitine puri®cation [71,72], more work is expected on the development of economical downstream processing of L L-carnitine.…”

Section: Discussionmentioning

confidence: 99%

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Microbial and enzymatic production of l-carnitine

Naidu

Lee

et al. 2000

Bioprocess Engineering

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L L-Carnitine (vitamin B T ) plays a vital role in the transportation of long-chain fatty acids into mitochondrial matrix in mammals. L L-Carnitine has a wide range of applications in pharmaceuticals, food products, and feed additives. Due to the increasing demand for L L-carnitine in food and pharmaceutical applications, production of this compound has become prominent. However, very little has been reported on the production of L L-carnitine. This review discusses the microbial and the enzymatic production of L L-carnitine from different starting materials (substrates).

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Microbial and enzymatic production of l-carnitine

Naidu

Lee

et al. 2000

Bioprocess Engineering

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“…In fact, conversion in the range of 90–95% and productivities of up to 5.4 g·L -1 ·h -1 have been reported in cell recycle reactors. Moreover, the process was scalable to up to 2500 L, but the production costs were high compared with the fed-batch operated process, despite the lower productivity attained (about 75% lower, 99% conversion) [ 84 ].…”

Section: Introductionmentioning

confidence: 99%

Production of L-carnitine by secondary metabolism of bacteria

et al. 2007

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The increasing commercial demand for L-carnitine has led to a multiplication of efforts to improve its production with bacteria. The use of different cell environments, such as growing, resting, permeabilized, dried, osmotically stressed, freely suspended and immobilized cells, to maintain enzymes sufficiently active for L-carnitine production is discussed in the text. The different cell states of enterobacteria, such as Escherichia coli and Proteus sp., which can be used to produce Lcarnitine from crotonobetaine or D-carnitine as substrate, are analyzed. Moreover, the combined application of both bioprocess and metabolic engineering has allowed a deeper understanding of the main factors controlling the production process, such as energy depletion and the alteration of the acetyl-CoA/CoA ratio which are coupled to the end of the biotransformation. Furthermore, the profiles of key central metabolic activities such as the TCA cycle, the glyoxylate shunt and the acetate metabolism are seen to be closely interrelated and affect the biotransformation efficiency. Although genetically modified strains have been obtained, new strain improvement strategies are still needed, especially in Escherichia coli as a model organism for molecular biology studies. This review aims to summarize and update the state of the art in L-carnitine production using E. coli and Proteus sp, emphasizing the importance of proper reactor design and operation strategies, together with metabolic engineering aspects and the need for feed-back between wet and in silico work to optimize this biotransformation.

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“…Table 4 is a very general overview and many variants of suspension cultures cannot be discussed here. For example the immobilisation of cells by filtration in combination with continuous culture is a powerful tool to reach outstanding productivities with mammalian and microbial cells if sterile operation can be achieved and the cell type allows extended number of cell divisions and generations Hoeks et al, 1992). Fig.…”

Section: Cultivation Optionsmentioning

confidence: 99%