Skip to main content
Log in

Performance and mechanism of co-culture of Monascus purpureus, Lacticaseibacillus casei, and Saccharomyces cerevisiae to enhance lovastatin production and lipid-lowering effects

  • Research Paper
  • Published:
Bioprocess and Biosystems Engineering Aims and scope Submit manuscript

Abstract

To facilitate lipid-lowering effects, a lovastatin-producing microbial co-culture system (LPMCS) was constituted with a novel strain Monascus purpureus R5 in combination with Lacticaseibacillus casei S5 and Saccharomyces cerevisiae J7, which increased lovastatin production by 54.21% compared with the single strain R5. Response Surface Methodology (RSM) optimization indicated lovastatin yield peaked at 7.43 mg/g with a fermentation time of 13.88 d, water content of 50.5%, and inoculum ratio of 10.27%. Meanwhile, lovastatin in LPMCS co-fermentation extracts (LFE) was qualitatively and quantitatively analyzed by Thin-Layer Chromatography (TLC) and High-Performance Liquid Chromatography (HPLC). Cellular experiments demonstrated that LFE exhibited no obvious cytotoxicity to L-02 cells and exhibited excellent biosafety. Most notably, high-dose LFE (100 mg/L) exhibited the highest reduction of lipid accumulation, total cholesterol, and triglycerides simultaneously in oleic acid-induced L-02 cells, which decreased by 71.59%, 38.64%, and 58.85% than untreated cells, respectively. Overall, LPMCS provides a potential approach to upgrade the lipid-lowering activity of Monascus-fermented products with higher health-beneficial effects.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4.
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Wang J, Zhao J, Yan C, Xi C, Wu C, Zhao J, Li F, Ding Y, Zhang R, Qi S, Li X, Liu C, Hou W, Chen H, Wang Y, Wu D, Chen K, Jiang H, Huang H, Liu H (2022) Identification and evaluation of a lipid-lowering small compound in preclinical models and in a Phase I trial. Cell Metab 34:667-680.e666. https://doi.org/10.1016/j.cmet.2022.03.006

    Article  CAS  PubMed  Google Scholar 

  2. Li H, Liang J, Han M, Wang X, Ren Y, Wang Y, Huang J, Li S, Liu C, Wang Z, Yue T, Gao Z (2022) Sequentially fermented dealcoholized apple juice intervenes fatty liver induced by high-fat diets via modulation of intestinal flora and gene pathways. Food Res Int 156:111180. https://doi.org/10.1016/j.foodres.2022.111180

    Article  CAS  PubMed  Google Scholar 

  3. Corpier CL, Jones PH, Suki WN, Lederer ED, Quinones MA, Schmidt SW, Young JB (1988) Rhabdomyolysis and renal injury with lovastatin use: report of two cases in cardiac transplant recipients. JAMA 260:239–241. https://doi.org/10.1001/jama.1988.03410020105038

    Article  CAS  PubMed  Google Scholar 

  4. Patel S (2016) Functional food red yeast rice (RYR) for metabolic syndrome amelioration: a review on pros and cons. World J Microbiol Biotechnol 32:87. https://doi.org/10.1007/s11274-016-2035-2

    Article  CAS  PubMed  Google Scholar 

  5. Ren R, Zeng H, Mei Q, Xu Z, Mazhar M, Qin L (2022) Effects of Monascus purpureus-fermented tartary buckwheat extract on the blood lipid profile, glucose tolerance and antioxidant enzyme activities in KM mice. J Cereal Sci 105:103465. https://doi.org/10.1016/j.jcs.2022.103465

    Article  CAS  Google Scholar 

  6. Dahiya D, Manuel JV, Nigam PS (2021) An overview of bioprocesses employing specifically selected microbial catalysts for & gamma;-aminobutyric acid production. Micro 9:2457. https://doi.org/10.3390/microorganisms9122457

    Article  CAS  Google Scholar 

  7. Huang Y-p, Li P, Du T, Du X-j, Wang S (2020) Protective effect and mechanism of Monascus-fermented red yeast rice against colitis caused by Salmonella enterica serotype Typhimurium ATCC 14028. Food Funct 11:6363–6375. https://doi.org/10.1039/D0FO01017K

    Article  CAS  PubMed  Google Scholar 

  8. Yang H, Pan R, Wang J, Zheng L, Li Z, Guo Q, Wang C (2021) Modulation of the gut microbiota and liver transcriptome by red yeast rice and monascus pigment fermented by purple monascus SHM1105 in rats fed with a high-fat diet. Front Pharmacol. https://doi.org/10.3389/fphar.2020.599760

    Article  PubMed  PubMed Central  Google Scholar 

  9. Lu Y, Ding H, Jiang X, Zhang H, Ma A, Hu Y, Li Z (2021) Effects of the extract from peanut meal fermented with Bacillus natto and Monascus on lipid metabolism and intestinal barrier function of hyperlipidemic mice. J Sci Food Agric 101:2561–2569. https://doi.org/10.1002/jsfa.10884

    Article  CAS  PubMed  Google Scholar 

  10. El-Bondkly AAM, El-Gendy MMAA, El-Bondkly AMA (2021) Construction of efficient recombinant strain through genome shuffling in marine endophytic fusarium sp. ALAA-20 for improvement lovastatin production using agro-industrial wastes. Arab J Sci Eng 46:175–190. https://doi.org/10.1007/s13369-020-04925-5

    Article  CAS  Google Scholar 

  11. Mouafi FE, Ibrahim GS, Abo Elsoud MM (2016) Optimization of lovastatin production from Aspergillus fumigatus. J Genet Eng Biotechnol 14:253–259. https://doi.org/10.1016/j.jgeb.2016.10.006

    Article  PubMed  PubMed Central  Google Scholar 

  12. Chang YN, Huang JC, Lee CC, Shih IL, Tzeng YM (2002) Use of response surface methodology to optimize culture medium for production of lovastatin by Monascus ruber. Enzyme Microb Technol 30:889–894. https://doi.org/10.1016/s0141-0229(02)00037-6

    Article  CAS  Google Scholar 

  13. Sieuwerts S, Bron PA, Smid EJ (2018) Mutually stimulating interactions between lactic acid bacteria and Saccharomyces cerevisiae in sourdough fermentation. LWT Food Sci Technol 90:201–206. https://doi.org/10.1016/j.lwt.2017.12.022

    Article  CAS  Google Scholar 

  14. Strazdina I, Klavins L, Galinina N, Shvirksts K, Grube M, Stalidzans E, Kalnenieks U (2021) Syntrophy of Crypthecodinium cohnii and immobilized Zymomonas mobilis for docosahexaenoic acid production from sucrose-containing substrates. J Biotechnol 338:63–70. https://doi.org/10.1016/j.jbiotec.2021.07.008

    Article  CAS  PubMed  Google Scholar 

  15. Viesser JA, Pereira GVD, Neto DPD, Rogez H, Goes-Neto A, Azevedo V, Brenig B, Aburjaile F, Soccol CR (2021) Co-culturing fructophilic lactic acid bacteria and yeast enhanced sugar metabolism and aroma formation during cocoa beans fermentation. Int J Food Microbiol. https://doi.org/10.1016/j.ijfoodmicro.2020.109015

    Article  PubMed  Google Scholar 

  16. Wang L, Bei Q, Wu Y, Liao W, Wu Z (2017) Characterization of soluble and insoluble-bound polyphenols from Psidium guajava L. leaves co-fermented with Monascus anka and Bacillus sp. and their bio-activities. J Funct Foods 32:149–159. https://doi.org/10.1016/j.jff.2017.02.029

    Article  CAS  Google Scholar 

  17. Chen G, Liu Y, Zeng JR, Tian XF, Bei Q, Wu ZQ (2020) Enhancing three phenolic fractions of oats (Avena sativa L.) and their antioxidant activities by solid-state fermentation with Monascus anka and Bacillus subtilis. J Cer Sci. https://doi.org/10.1016/j.jcs.2020.102940

    Article  Google Scholar 

  18. Reis SA, Conceição LL, Rosa DD, Siqueira NP, Peluzio MCG (2017) Mechanisms responsible for the hypocholesterolaemic effect of regular consumption of probiotics. Nutr Res Rev 30:36–49. https://doi.org/10.1017/S0954422416000226

    Article  CAS  PubMed  Google Scholar 

  19. Luo D, Li X, Zhao L, Chen G (2021) Regulation of phenolic release in corn seeds (Zea mays L.) for improving their antioxidant activity by mix-culture fermentation with Monascus anka, Saccharomyces cerevisiae and Bacillus subtilis. J Biotechnol 325:334–340. https://doi.org/10.1016/j.jbiotec.2020.10.002

    Article  CAS  PubMed  Google Scholar 

  20. Zhang B-B, Lu L-P, Xu G-R (2015) Why solid-state fermentation is more advantageous over submerged fermentation for converting high concentration of glycerol into Monacolin K by Monascus purpureus 9901: a mechanistic study. J Biotechnol 206:60–65. https://doi.org/10.1016/j.jbiotec.2015.04.011

    Article  CAS  PubMed  Google Scholar 

  21. Chayawat J, Jareonkitmongkol S, Songsasen A, Isariyodom S, Yongsmith B (2008) Rice solid fermentation of monacolins and pigments by Monascus kaoliang KB9 and its color mutants. J Biotechnol 136:S750. https://doi.org/10.1016/j.jbiotec.2008.07.1784

    Article  Google Scholar 

  22. Panda BP, Javed S, Ali M (2010) Optimization of fermentation parameters for higher lovastatin production in red mold rice through co-culture of Monascus purpureus and Monascus ruber. Food Bioproe Tech 3:373–378. https://doi.org/10.1007/s11947-008-0072-z

    Article  CAS  Google Scholar 

  23. Dikshit R, Tallapragada P (2016) Statistical optimization of lovastatin and confirmation of nonexistence of citrinin under solid-state fermentation by Monascus sanguineus. J Food Drug Anal 24:433–440. https://doi.org/10.1016/j.jfda.2015.11.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Chen L, Liu L, Li C, Hu C, Su F, Liu R, Zeng M, Zhao D, Liu J, Guo Y, Long J (2017) A mix of apple pomace polysaccharide improves mitochondrial function and reduces oxidative stress in the liver of high-fat diet-induced obese mice. Mol Nutr Food Res 61:1600433. https://doi.org/10.1002/mnfr.201600433

    Article  CAS  Google Scholar 

  25. Xie CF, Chen Z, Zhang CF, Xu X, Jin JB, Zhan WH, Han TY, Wang JB (2016) Dihydromyricetin ameliorates oleic acid-induced lipid accumulation in L02 and HepG2 cells by inhibiting lipogenesis and oxidative stress. Life Sci 157:131–139. https://doi.org/10.1016/j.lfs.2016.06.001

    Article  CAS  PubMed  Google Scholar 

  26. Choi D-H, Han J-H, Hong M, Lee S-Y, Lee S-U, Kwon T-H (2022) Antioxidant and lipid-reducing effects of Rosa rugosa root extract in 3T3-L1 cell. Food Sci Biotechnol 31:121–129. https://doi.org/10.1007/s10068-021-01018-3

    Article  CAS  PubMed  Google Scholar 

  27. Panda B, Javed S, Ali M (2009) Statistical analysis and validation of process parameters influencing lovastatin production by Monascus purpureus MTCC 369 under solid-state fermentation. Biotechnol Bioprocess Eng 14:123–127. https://doi.org/10.1007/s12257-008-0016-5

    Article  CAS  Google Scholar 

  28. Suresh G, Balasubramanian B, Ravichandran N, Ramesh B, Kamyab H, Velmurugan P, Siva GV, Ravi AV (2021) Bioremediation of hexavalent chromium-contaminated wastewater by Bacillus thuringiensis and Staphylococcus capitis isolated from tannery sediment. Biomass Conver Biore 11:383–391. https://doi.org/10.1007/s13399-020-01259-y

    Article  CAS  Google Scholar 

  29. Darwesh OM, Matter IA, Almoallim HS, Alharbi SA, Oh Y-K (2020) Isolation and optimization of Monascus ruber OMNRC45 for red pigment production and evaluation of the pigment as a food colorant. Appl Sci 10:8867. https://doi.org/10.3390/app10248867

    Article  CAS  Google Scholar 

  30. Wu Y, Li S, Tao Y, Li D, Han Y, Show PL, Wen G, Zhou J (2021) Fermentation of blueberry and blackberry juices using Lactobacillus plantarum, Streptococcus thermophilus and Bifidobacterium bifidum: growth of probiotics, metabolism of phenolics, antioxidant capacity in vitro and sensory evaluation. Food Chem 348:129083. https://doi.org/10.1016/j.foodchem.2012.06.048

    Article  CAS  Google Scholar 

  31. Balraj J, Jairaman K, Kalieswaran V, Jayaraman A (2018) Bioprospecting lovastatin production from a novel producer Cunninghamella blakesleeana. 3 Biotech 8:359. https://doi.org/10.1007/s13205-018-1384-y

    Article  PubMed  PubMed Central  Google Scholar 

  32. Subhagar S, Aravindan R, Viruthagiri T (2009) Response surface optimization of mixed substrate solid state fermentation for the production of lovastatin by Monascus purpureus. Eng Life Sci 9:303–310. https://doi.org/10.1002/elsc.200900022

    Article  CAS  Google Scholar 

  33. Marič A, Skočaj M, Likar M, Sepčić K, Cigić IK, Grundner M, Gregori A (2019) Comparison of lovastatin, citrinin and pigment production of different Monascus purpureus strains grown on rice and millet. J Food Sci Technol 56:3364–3373. https://doi.org/10.1007/s13197-019-03820-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Ketkaeo S, Sanpamongkolchai W, Morakul S, Baba S, Kobayashi G, Goto M (2020) Induction of mutation in <i>Monascus purpureus</i> isolated from Thai fermented food to develop low citrinin-producing strain for application in the red koji industry. JGAM 66:163–168. https://doi.org/10.2323/jgam.2019.04.008

    Article  CAS  Google Scholar 

  35. Xu B-J, Wang Q-J, Jia X-Q, Sung C-K (2005) Enhanced lovastatin production by solid state fermentation ofMonascus ruber. Biotechnol Bioprocess Eng 10:78–84. https://doi.org/10.1007/BF02931187

    Article  CAS  Google Scholar 

  36. Rahayu YYS, Yoshizaki Y, Yamaguchi K, Okutsu K, Futagami T, Tamaki H, Sameshima Y, Takamine K (2017) Key volatile compounds in red koji-shochu, a Monascus-fermented product, and their formation steps during fermentation. Food Chem 224:398–406. https://doi.org/10.1016/j.foodchem.2016.12.005

    Article  CAS  PubMed  Google Scholar 

  37. Zhang YF, Dai ZM, Zhou ZC, Yin HQ, Zhang M, Zhang HT, Liu YJ, Li Q, Nan XL, Liu XD, Meng DL (2021) Development of the yeast and lactic acid bacteria co-culture agent for atmospheric ammonia removing: Genomic features and on-site applications. Ecotoxicol Environ Saf. https://doi.org/10.1016/j.ecoenv.2021.112287

    Article  PubMed  PubMed Central  Google Scholar 

  38. Ghosh K, Ray M, Adak A, Dey P, Halder SK, Das A, Jana A, Parua S, Das Mohapatra PK, Pati BR, Mondal KC (2015) Microbial, saccharifying and antioxidant properties of an Indian rice based fermented beverage. Food Chem 168:196–202. https://doi.org/10.1016/j.foodchem.2014.07.042

    Article  CAS  PubMed  Google Scholar 

  39. Shimizu H, Mizuguchi T, Tanaka E, Shioya SJA, Microbiology E (1999) Nisin production by a mixed-culture system consisting of Lactococcus lactis and Kluyveromyces marxianus. Appl Environ Microbiol 65:3134. https://doi.org/10.1128/AEM.65.7.3134-3141.1999

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Astuti DI, Noviana Z (2014) Optimization of fermented tofu with high isoflavone content through variation of inoculum percentages and ratios of lactobacillus plantarum, lactobacillus acidophilus, and leuconostoc mesenteroides. J Math Fundam Sci. https://doi.org/10.5614/j.math.fund.sci.2013.45.3.5

    Article  Google Scholar 

  41. Suraiya S, Kim JH, Tak JY, Siddique MP, Young CJ, Kim JK, Kong IS (2018) Influences of fermentation parameters on lovastatin production by Monascus purpureus using Saccharina japonica as solid fermented substrate. LWT Food Sci Technol 92:1–9. https://doi.org/10.1016/j.lwt.2018.02.013

    Article  CAS  Google Scholar 

  42. Bruno-Bárcena JM, Azcárate-Peril MA, Hassan HM (2010) Role of antioxidant enzymes in bacterial resistance to organic acids. Appl Environ Microbiol 76:2747–2753. https://doi.org/10.1128/AEM.02718-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Wu A, Li L, Zhang S, Lin Q, Liu J (2022) Optimization of the hongqu starter preparation process for the manufacturing of red mold rice with high gamma-aminobutyric acid production by solid-state fermentation. Biotech App Biochem. https://doi.org/10.1002/bab.2370

    Article  Google Scholar 

  44. Zhang B-B, Xing H-B, Jiang B-J, Chen L, Xu G-R, Jiang Y, Zhang D-Y (2018) Using millet as substrate for efficient production of monacolin K by solid-state fermentation of Monascus ruber. J Biosci Bioeng 125:333–338. https://doi.org/10.1016/j.jbiosc.2017.10.011

    Article  CAS  PubMed  Google Scholar 

  45. Sayyad SA, Panda BP, Javed S, Ali M (2007) Optimization of nutrient parameters for lovastatin production by Monascus purpureus MTCC 369 under submerged fermentation using response surface methodology. Appl Microbiol Biotechnol 73:1054–1058. https://doi.org/10.1007/s00253-006-0577-1

    Article  CAS  PubMed  Google Scholar 

  46. Javed S, Meraj M, Mahmood S, Hameed A, Naz F, Hassan S, Irfan R (2017) Biosynthesis of lovastatin using agro-industrial wastes as carrier substrates. Trop J Pharm Res 16:263–269. https://doi.org/10.4314/tjpr.v16i2.1

    Article  CAS  Google Scholar 

  47. Seenivasan A, Gummadi SN, Panda T (2017) Comparison of the elution characteristics of individual forms of lovastatin in both isocratic and gradient modes and HPLC-PDA method development for pure and fermentation-derived lovastatin. Prep Biochem Biotechnol 47:901–908. https://doi.org/10.1080/10826068.2017.1365239

    Article  CAS  PubMed  Google Scholar 

  48. Chen C-H, Yang J-C, Uang Y-S, Lin C-J (2013) Improved dissolution rate and oral bioavailability of lovastatin in red yeast rice products. Int J Pharm 444:18–24. https://doi.org/10.1016/j.ijpharm.2013.01.028

    Article  CAS  PubMed  Google Scholar 

  49. Oi S, Haneda T, Osaki J, Kashiwagi Y, Nakamura Y, Kawabe J, Kikuchi K (1999) Lovastatin prevents angiotensin II-induced cardiac hypertrophy in cultured neonatal rat heart cells. Eur J Pharmacol 376:139–148. https://doi.org/10.1016/s0014-2999(99)00282-4

    Article  CAS  PubMed  Google Scholar 

  50. Lye HS, Kuan CY, Ewe JA, Fung WY, Liong MT (2009) The improvement of hypertension by probiotics: effects on cholesterol, diabetes, renin, and phytoestrogens. Int J Mol Sci 10:3755–3775. https://doi.org/10.3390/ijms10093755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Suraiya S, Choi YB, Park HD, Jang WJ, Lee HH, Kong IS (2019) Saccharina japonica fermented by Monascus spp. inhibit adipogenic differentiation and gene expression analyzed by real-time PCR (Q-PCR) in 3T3-L1 cell. J Funct Foods 55:371–380. https://doi.org/10.1016/j.jff.2019.02.043

    Article  CAS  Google Scholar 

  52. Gerard P (2013) Metabolism of cholesterol and bile acids by the gut microbiota. Pathogens (Basel, Switzerland) 3:14–24. https://doi.org/10.3390/pathogens3010014

    Article  CAS  PubMed  Google Scholar 

  53. Jeon T, Hwang SG, Hirai S, Matsui T, Yano H, Kawada T, Lim BO, Park DK (2004) Red yeast rice extracts suppress adipogenesis by down-regulating adipogenic transcription factors and gene expression in 3T3-L1 cells. Life Sci 75:3195–3203. https://doi.org/10.1016/j.lfs.2004.06.012

    Article  CAS  PubMed  Google Scholar 

  54. Rosen ED, Walkey CJ, Puigserver P, Spiegelman BM (2000) Transcriptional regulation of adipogenesis. Genes Dev 14:1293–1307. https://doi.org/10.1002/cphy.c160022

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (Grant No. 51978576 and 42207021), the Provincial Key Research and Development Program of Sichuan (2021YJ0495), the Science and Technology Project of Sichuan Tobacco Company of China National Tobacco Corporation (SCYC202109), the Key Research and Development Plant of Sichuan Province (2023YFSY0011, 2023ZHCG0058), the Natural Science Foundation of Sichuan (2022NSFSC1670), the technical Innovation Research and Development Project of Chengdu (2022-YF05-00269-SN, 2022-YF05-00909-SN), and the Fundamental Research Funds for the Central Universities (2682022CX057). The authors would also like to thank Dr. Weizhen Fang of the Analysis and Testing Center, Southwest Jiaotong University, for the technical support.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Zhongping Qiu.

Ethics declarations

Conflict of interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOC 4916 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, M., Wang, Q., Zhang, H. et al. Performance and mechanism of co-culture of Monascus purpureus, Lacticaseibacillus casei, and Saccharomyces cerevisiae to enhance lovastatin production and lipid-lowering effects. Bioprocess Biosyst Eng 46, 1411–1426 (2023). https://doi.org/10.1007/s00449-023-02903-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00449-023-02903-3

Keywords

Navigation