Proteomic insights into the polyketide pathways of Monascus
Date Issued
2011
Date
2011
Author(s)
Tan, Ya-Yun
Abstract
Monascus species produce several potent bioactive metabolites through polyketide secondary metabolic pathways. However, there is little known about the metabolic regulation processes of Monascus. We observed that four strains, M. purpureus BCRC 31615, M. ruber BCRC 31534, M. pilosus BCRC 31526 and M. purpureus NTU 568, have different expression pattern of secondary metabolites inherently. M. purpureus NTU 568, isolated by our research group, could produce higher amount of yellow pigments than other Monascus strains but lower citrinin compared with M. purpureus BCRC 31615. On the other hand, M. ruber BCRC 31534 and M. pilosus BCRC 31526 produced red pigment instead of yellow pigment and citrinin in dextrin-MSG-mineral (DMM) medium cultivation. Furthermore, the production level of red pigment was higher in M. ruber BCRC 31534 compared with M. pilosus BCRC 31526. Assuming the different expression pattern of secondary metabolites might reflect on protein expression level of Monascus species identically, in order to understand the regulatory processes of polyketide pathway in Monascus, we used a comparative proteomic approach to identify proteins with significant expression change among different strains. The protein expression level of monooxygenase, the enzyme that might correlated with polyketide synthases, is higher in M. purpureus NTU 568 compared with M. purpureus BCRC 31615; meanwhile, mevalonate secondary metabolic pathway might be inactive. The proteins involved in branched-chain amino acids degradation, together with aldehyde dehydrogenase (ALDH), were expressed higher level basically in M. purpureus NTU 568. Malonyl-CoA and butanoyl-CoA, synthesized through BCAA degradation, and acetate, produced by ALDH, could be starter units of polyketides. However, after cultured in DMM medium containing 4% EtOH, M. purpureus NTU 568’s BCAA degradation and ALDH expression level were inversely down-regulated, the ability of producing yellow pigment and citrinin was inhibited, and heat shock response was induced as well. Furthermore, both polyketide synthesis related proteins fatty acid synthase and epoxide hydrolase and shikimate secondary metabolic pathway were inhibited by EtOH treatment. M. ruber BCRC 31534, higher red pigment producing strain, has higher expression level of pyruvate dehydrogenase complex compared with M. pilosus BCRC 31526, might resulted in increasing acetyl-CoA pool in cell. Moreover, the decreasing protein level of dihydroxyacetone kinase which participated in glycerol metabolism might result in propionyl-CoA synthesis. These results suggested that higher production of polyketide metabolites result from not only protein expression level of polyketide synthesis pathway, but also elevating starter units from primary metabolism as substrates for polyketide synthesis. This study provides further understanding of the polyketide secondary metabolism of Monascus, together with useful information to improve the production of bioactive secondary metabolites in Monascus species.
Subjects
polyketide pathway
Monascus
citrinin
monascin
ankaflavin
Type
thesis
File(s)![Thumbnail Image]()
Loading...
Name
ntu-100-R98b47104-1.pdf
Size
23.32 KB
Format
Adobe PDF
Checksum
(MD5):f63dcffd12e7609ead7e10eb7cf447b3