Metabolic Engineering of Saccharomyces cerevisiae for Vitamin B5 Production

Abstract

Vitamin B5, also called d-pantothenic acid, is an essential vitamin in the human body and is widely used in pharmaceuticals, nutritional supplements, food, and cosmetics. However, few studies have investigated the microbial production of d-pantothenic acid, especially in Saccharomyces cerevisiae. By employing a systematic optimization strategy, we screened seven key genes in d-pantothenic acid biosynthesis from diverse species, including bacteria, yeast, fungi, algae, plants, animals, etc., and constructed an efficient heterologous d-pantothenic acid pathway in S. cerevisiae. By adjusting the copy number of the pathway modules, knocking out the endogenous bypass gene, balancing NADPH utilization, and regulating the GAL inducible system, a high-yield d-pantothenic acid-producing strain, DPA171, which can regulate gene expression using glucose, was constructed. By optimizing fed-batch fermentation, DPA171 produced 4.1 g/L d-pantothenic acid, which is the highest titer in S. cerevisiae to date. This study provides guidance for the development of vitamin B5 microbial cell factories.

Combining Metabolic Engineering and Lipid Droplet Assembly to Achieve Campesterol Overproduction in Saccharomyces cerevisiae

“…As a eukaryotic model microorganism, the development of high-density S. cerevisiae fermentation strains has been a long-term goal pursued by the fermentation industry. − The biggest advantage of high-density fermentation is that each parameter value can be finely controlled during the fermentation process to maintain optimal fermentation conditions for cell growth and the production of the target product. , On the one hand, the productivity of the final product can be maximized, and on the other hand, the volume of the fermentation tank can be fully utilized and separation costs can be reduced. , In the present study, due to the knockout of the ERG5 gene, the synthesis pathway of ergosterol in S. cerevisiae has been disrupted.…”

Engineered ketoreductase-catalyzed stereoselective reduction of ethyl 2′-ketopantothenate and its analogues: chemoenzymatic synthesis of d-pantothenic acid

“…[1][2][3][4] The physiological importance of D-PaA mainly results from it being the critical precursor in the biosynthesis of coenzyme A and acyl carrier protein. [1][2][3][4][5] Various diseases such as alopecia and neurodegenerative diseases could occur under the deficiency of D-PaA. 5,6 Given the physiological significance of D-PaA, calcium pantothenate, the commercial form of D-PaA, has been broadly applied as an ingredient or additive in pharmaceuticals, cosmetics, feed, and food.…”

“…[1][2][3][4][5] Various diseases such as alopecia and neurodegenerative diseases could occur under the deficiency of D-PaA. 5,6 Given the physiological significance of D-PaA, calcium pantothenate, the commercial form of D-PaA, has been broadly applied as an ingredient or additive in pharmaceuticals, cosmetics, feed, and food. [1][2][3][4][5][6][7] With the annual production capacity reaching greater than 23 000 tons, the global market value of calcium pantothenate has been estimated to be over one billion US dollars.…”

“…5,6 Given the physiological significance of D-PaA, calcium pantothenate, the commercial form of D-PaA, has been broadly applied as an ingredient or additive in pharmaceuticals, cosmetics, feed, and food. [1][2][3][4][5][6][7] With the annual production capacity reaching greater than 23 000 tons, the global market value of calcium pantothenate has been estimated to be over one billion US dollars. 8 In the current industrial manufacture route to D-PaA (route I, Fig.…”

Discovery and Engineering of a Novel Bacterial L-Aspartate α-Decarboxylase for Efficient Bioconversion

“…L-aspartate α-decarboxylase (ADC, EC 4. 1.1.11), a lyase that catalyzes L-aspartate to β-alanine and CO 2 , is an important metabolic enzyme involving the metabolic pathway of β-alanine and D-pantothenic acid [1][2][3][4]. In biotechnology, ADC has been widely applied to synthesize β-alanine and D-pantothenic acid via enzymatic transformation and metabolic engineering.…”