Optimal pH control strategy for high-level production of long-chain α,ω-dicarboxylic acid by Candida tropicalis

Shuchen, Liu; Li, Chun; Fang, Xiangchen; Zhu-an, Cao

doi:10.1016/j.enzmictec.2003.09.001

Cited by 60 publications

(48 citation statements)

References 13 publications

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“…The inner pH of the cell, as well as aeration, both affect the induction of yeast CYP monooxygenase and CYP reductase [10]. Studies show that a higher dissolved oxygen (DO) level can remarkably improve P450 activity [99,100]. This level was kept at 80% saturation for LCDCA production from C. ropiclais [14].…”

Section: Discussionmentioning

confidence: 99%

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Combinatorial Engineering of Yarrowia lipolytica as a Promising Cell Biorefinery Platform for the de novo Production of Multi-Purpose Long Chain Dicarboxylic Acids

2017

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This proof-of-concept study establishes Yarrowia lipolytica (Y. lipolytica) as a whole cell factory for the de novo production of long chain dicarboxylic acid (LCDCA-16 and 18) using glycerol as the sole source of carbon. Modification of the fatty acid metabolism pathway enabled creating a pool of fatty acids in a β-oxidation deficient strain. We then selectively upregulated the native fatty acid ω-oxidation pathway for the enhanced terminal oxidation of the endogenous fatty acid precursors. Nitrogen-limiting conditions and leucine supplementation were employed to induce fatty acid biosynthesis in an engineered Leu -modified strain. Our genetic engineering strategy allowed a minimum production of 330 mg/L LCDCAs in shake flask. Scale up to a 1-L bioreactor increased the titer to 3.49 g/L. Our engineered yeast also produced citric acid as a major by-product at a titer of 39.2 g/L. These results provide basis for developing Y. lipolytica as a safe biorefinery platform for the sustainable production of high-value LCDCAs from non-oily feedstock.

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Section: Discussionmentioning

confidence: 99%

“…Transport of LCDCAs out of the cell can improve P450 activity [100] and simplify recovery for an enhanced downstream process at a lower cost. Our engineered strain showed good secretion efficiency, since more than half of the synthetized monomers were found in the media [102].…”

Section: Discussionmentioning

confidence: 99%

Combinatorial Engineering of Yarrowia lipolytica as a Promising Cell Biorefinery Platform for the de novo Production of Multi-Purpose Long Chain Dicarboxylic Acids

2017

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“…It is important to find the balance between limited DCA production at low pH and negative effects on cell viability at high pH values. Additionally to pH, also the dissolved oxygen and the inner pH of the cells seem to influence the activity of CYP monooxygenases during DCA production phase [113]. Via a reduction of intracellular levels of accumulated DCA, which inhibit the CYP system, it could be possible to further increase CYP activity and DCA production [23,113].…”

Section: Bioprocess Engineeringmentioning

confidence: 98%

“…In case of production of DCA with C. tropicalis defined mineral nutrient [106,108,115,116] as well as so-called ''semi-defined'' media [11,73,109,110,113,117,118] were described. In our studies we described the use of different media (complex and mineral salt) and also feeding strategies like fed batch with constant or exponential feed to increase microbial biomass for higher cell density of C. tropicalis ATCC20962, which leads to a higher production rate of 1,18-octadecenedioic acid [119].…”

Section: Bioprocess Engineeringmentioning

confidence: 99%

Biotechnological synthesis of long‐chain dicarboxylic acids as building blocks for polymers

Huf

Krügener

Hirth

et al. 2011

Eur. J. Lipid Sci. Technol.

121

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An important field in sustainable industrial chemistry is the development of new applications for fats and oils. One of the promising applications is the use of fatty acid derivatives, e.g. dicarboxylic acid (DCA), as polymer building blocks. In contrast to conventional plastics, bioplastics are polymers derived from renewable biomass sources. In addition to their contribution to the conservation of fossil resources and reduction in CO2 emissions by waste incineration, many bioplastics are biodegradable. The majority of industrial DCA production for polyamide (PA) and polyester (PE) synthesis is still done via chemical synthesis. While short-chain DCA can be synthesized in high yields, costs of long-chain DCA production rise significantly due to the generation of various by-products and are connected mostly to a costly purification. Thus biotechnology provides novel biochemical approaches for long-chain DCA synthesis that can provide an eco-efficient process alternative . In the present article, strategies for the development of high-level production strains for long-chain DCA are illustrated. Basic strategies for strain development, in order to achieve an effective enrichment of DCA, require the knowledge of the respective biochemical pathways. These are discussed in detail. Furthermore an overview of fermentation strategies and characteristics of corresponding polymers is given

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“…The best performance among the processes, in relation to the presented targets, is found using an unspecified P450 in a growing natural P450 expressing mutant strain of Candida tropicalis. This uncharacterized P450 is converting n-tridecane to the corresponding dicarboxylic acid in a batch process where fermentation and conversion were separated into two steps, although in the same fermenter (Liu et al 2004). A step-wise addition of alkane and optimized pH profile, by gradual increase during the production phase, were applied to the process.…”

Section: Lewis Cell Experimentsmentioning

confidence: 99%

Guidelines for development and implementation of biocatalytic P450 processes

Lundemo

Woodley

2015

Appl Microbiol Biotechnol

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Biocatalytic reactions performed by cytochrome P450 monooxygenases are interesting in pharmaceutical research since they are involved in human drug metabolism. Furthermore, they are potentially interesting as biocatalysts for synthetic chemistry because of the exquisite selectivity of the chemistry they undertake. For example, selective hydroxylation can be undertaken on a highly functionalized molecule without the need for functional group protection. Recent progress in the discovery of novel P450s as well as protein engineering of these enzymes strongly encourages further development of their application, including use in synthetic processes. The biological characteristics of P450s (e.g., cofactor dependence) motivate the use of whole-cell systems for synthetic processes, and those processes implemented in industry are so far dominated by growing cells and native host systems. However, for an economically feasible process, the expression of P450 systems in a heterologous host with sufficient biocatalyst yield (g/g cdw) for non-growing systems or space-time yield (g/L/h) for growing systems remains a major challenge. This review summarizes the opportunities to improve P450 whole-cell processes and strategies in order to apply and implement them in industrial processes, both from a biological and process perspective. Indeed, a combined approach of host selection and cell engineering, integrated with process engineering, is suggested as the most effective route to implementation.

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Optimal pH control strategy for high-level production of long-chain α,ω-dicarboxylic acid by Candida tropicalis

Cited by 60 publications

References 13 publications

Combinatorial Engineering of Yarrowia lipolytica as a Promising Cell Biorefinery Platform for the de novo Production of Multi-Purpose Long Chain Dicarboxylic Acids

Combinatorial Engineering of Yarrowia lipolytica as a Promising Cell Biorefinery Platform for the de novo Production of Multi-Purpose Long Chain Dicarboxylic Acids

Biotechnological synthesis of long‐chain dicarboxylic acids as building blocks for polymers

Guidelines for development and implementation of biocatalytic P450 processes

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