Production of lovastatin examined by an integrated approach based on chemometrics and DOSY‐NMR

Abstract

Microbial secondary metabolites are one of the sources of therapeutic molecules in the pharmaceutical industry. Product quality and high yields of secondary metabolites are the main goals for the commercial success of a fermentation process. Our novel approach was based on the decision-tree algorithm to determine the key variables correlated with the process outcome and on DOSY-NMR to identify both co-metabolites and impurities, and it improves fermentation systems and speeds up bioprocess development. The approach has been validated in the case of lovastatin production from Aspergillus terreus.

Marilones A–C, phthalides from the sponge-derived fungus Stachylidium sp.

“…In terms of biosynthesis, i.e., polyketide metabolism, this substitution is most unusual for phthalides and, to the best of our knowledge, it was only found once in dimethoxydimethylphthalide (DDP) [12]. …”

Lovastatin biosynthesis by Aspergillus terreus with the simultaneous use of lactose and glycerol in a discontinuous fed-batch culture

“…glucose, lactose, maltodextrin and starch for their fedbatch culture. Manzoni et al (1998) and Bradamante et al (2002) added glycerol in the late idiophase to the media containing other carbon sources.…”

Bioprocess Engineering Aspects of the Cultivation of a Lovastatin Producer Aspergillus terreus

“…; mass transfer coefficients k L a depend on the morphological form of the hyphae: dispersed or pelleted 12 Rodriguez Porcel et al [60] Lovastatin formation is enhanced in fed-batch and semicontinuous bioreactor (with biomass retention), if fed with non-growth-promoting medium 13 Gupta et al [30] Correlation between morphology and rheology of A. terreus cultivation broths 14 Bizukojc and Ledakowicz [8] Unstructured kinetic model for A. terreus growth and lovastatin formation on the single carbon substrate (lactose) 15 Bizukojc and Ledakowicz [9] Determination of lovastatin and (+)-geodin (by-product) formation kinetics in conjunction with carbon substrate uptake (continued)…”