Lovastatin production: From molecular basis to industrial process optimization

Mulder, Kelly Cristina Leite; Mulinari, Flávia Furtado; Franco, Octávio L.; Soares, Maria S.F.; Magalhães, Beatriz Simas; Parachin, Nádia Skorupa

doi:10.1016/j.biotechadv.2015.04.001

Cited by 110 publications

(96 citation statements)

References 98 publications

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“…Due to their versatile metabolism, those fungi are one of the most prolific sources of enzymes, organic acids and secondary metabolites (SM) with biomedical and biotechnological interests [1][2][3][4]. Already described as non-mycotoxins producer in comparison to A. niger [5][6][7][8][9], A. tubingensis, which is part of the A. niger clade of the black Aspergilli, represents a good alternative for metabolites production in industrial fermentation and is already used for some applications [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Whole-genome sequencing of Aspergillus tubingensis G131 and overview of its secondary metabolism potential

Choque

Klopp²,

Valière³

et al. 2018

BMC Genomics

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Background: Black Aspergilli represent one of the most important fungal resources of primary and secondary metabolites for biotechnological industry. Having several black Aspergilli sequenced genomes should allow targeting the production of certain metabolites with bioactive properties. Results: In this study, we report the draft genome of a black Aspergilli, A. tubingensis G131, isolated from a French Mediterranean vineyard. This 35 Mb genome includes 10,994 predicted genes. A genomic-based discovery identifies 80 secondary metabolites biosynthetic gene clusters. Genomic sequences of these clusters were blasted on 3 chosen black Aspergilli genomes: A. tubingensis CBS 134.48, A. niger CBS 513.88 and A. kawachii IFO 4308. This comparison highlights different levels of clusters conservation between the four strains. It also allows identifying seven unique clusters in A. tubingensis G131. Moreover, the putative secondary metabolites clusters for asperazine and naphthogamma-pyrones production were proposed based on this genomic analysis. Key biosynthetic genes required for the production of 2 mycotoxins, ochratoxin A and fumonisin, are absent from this draft genome. Even if intergenic sequences of these mycotoxins biosynthetic pathways are present, this could not lead to the production of those mycotoxins by A. tubingensis G131.

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Section: Introductionmentioning

confidence: 99%

Whole-genome sequencing of Aspergillus tubingensis G131 and overview of its secondary metabolism potential

Choque

Klopp²,

Valière³

et al. 2018

BMC Genomics

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“…Several studies has been reported on the optimization of lovastatin production from Monascus sp. [13,[21][22][23][24] . In 2002, Chang et al [21] proposed a complex medium for M. ruber.…”

Section: Research Papermentioning

confidence: 99%

Cellular Localization and Production of Lovastatin from Monascus purpureus

Seenivasan¹,

Venkatesan²,

Tapobrata³

2018

pharmaceutical-sciences

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Seenivasan, et al.: Studies on Biosynthesis of LovastatinLovastatin is the first FDA-approved antihypercholesterolemic drug for the treatment of cardiovascular diseases. Monascus purpureus is one of the safest molds for the production of lovastatin that has been used in the preparation of Chinese medicine Red-yeast rice. This investigation dealt with the effect of both static and dynamic culture conditions on the morphological change and localization of lovastatin in Monascus purpureus. In dynamic culture condition, pellet morphology was observed and the maximum intra-and extra-cellular components of lovastatin including both β-hydroxy acid and lactone forms were 1043.45 and 207.94 μg/l, respectively. Filamentous (mat) form of morphology was observed in the static culture condition and the intra-and extracellular concentration of lovastatin were 677.9 and 789.2 μg/l, respectively. Taguchi's L 12 (11 2 ) orthogonal arrays was employed to find the optimal conditions for the submerged production of lovastatin and for the growth of Monascus purpureus. Three physical and five chemical variables were considered in the current experimental study. The maximum production of lovastatin was observed to be 3.66 mg/l. Among the chemical parameters, MnSO 4 and MgSO 4 were the most significant parameters for the production of lovastatin. Physical parameters, viz., agitation rate and temperature, were also equally significant for the production of lovastatin. Ammonium chloride was the most significant parameter among the variables studied for the growth of Monascus purpureus, followed by glucose and phosphorous sources (KH 2 PO 4 ). Statistical analysis showed that those parameters were significant with more than 99 % confidence (p<0.01).

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“…The biosynthesis of lovastatin is controlled within the regulatory framework of secondary metabolism (Mulder et al 2015). Regulation of fungal secondary metabolism involves a number of global and cluster-specific regulators, e.g.…”

Section: Biosynthesismentioning

confidence: 99%

“…Thus, the aim of this mini-review is to outline the similarities and differences with respect to the conditions favoring the production of lovastatin and itaconic acid by A. terreus . For the purpose of comparison, only the selected aspects of biosynthesis are discussed here, however the readers may consult the previous reviews on the production of lovastatin (Barrios-Gonzalez and Miranda 2010; Bizukojc and Ledakowicz 2015; Manzoni and Rollini 2002; Mulder et al 2015; Subhan et al 2016) and itaconic acid (Klement and Buchs 2013; Okabe et al 2009; Steiger et al 2013; Willke and Vorlop 2001) for further insights. While the influence of the respective parameters on the productivity of the process is always strain-specific and depends on the applied cultivation strategy, certain generalizations can still be made to open the door for the comparative discussion on lovastatin and itaconic acid production.…”

Section: Introductionmentioning

confidence: 99%

Production of lovastatin and itaconic acid by Aspergillus terreus: a comparative perspective

Boruta

Bizukojć

2017

World J Microbiol Biotechnol

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Aspergillus terreus is a textbook example of an industrially relevant filamentous fungus. It is used for the biotechnological production of two valuable metabolites, namely itaconic acid and lovastatin. Itaconic acid serves as a precursor in polymer industry, whereas lovastatin found its place in the pharmaceutical market as a cholesterol-lowering statin drug and a precursor for semisynthetic statins. Interestingly, their biosynthetic gene clusters were shown to reside in the common genetic neighborhood. Despite the genomic proximity of the underlying biosynthetic genes, the production of lovastatin and itaconic acid was shown to be favored by different factors, especially with respect to pH values of the broth. While there are several reviews on various aspects of lovastatin and itaconic acid production, the survey on growth conditions, biochemistry and morphology related to the formation of these two metabolites has never been presented in the comparative manner. The aim of the current review is to outline the correlations and contrasts with respect to process-related and biochemical discoveries regarding itaconic acid and lovastatin production by A. terreus.

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Lovastatin production: From molecular basis to industrial process optimization

Cited by 110 publications

References 98 publications

Whole-genome sequencing of Aspergillus tubingensis G131 and overview of its secondary metabolism potential

Whole-genome sequencing of Aspergillus tubingensis G131 and overview of its secondary metabolism potential

Cellular Localization and Production of Lovastatin from Monascus purpureus

Production of lovastatin and itaconic acid by Aspergillus terreus: a comparative perspective

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