Polyamines Upregulate Cephalosporin C Production and Expression of β-Lactam Biosynthetic Genes in High-Yielding Acremonium chrysogenum Strain

Abstract

The high-yielding production of pharmaceutically significant secondary metabolites in filamentous fungi is obtained by random mutagenesis; such changes may be associated with shifts in the metabolism of polyamines. We have previously shown that, in the Acremonium chrysogenum cephalosporin C high-yielding strain (HY), the content of endogenous polyamines increased by four- to five-fold. Other studies have shown that the addition of exogenous polyamines can increase the production of target secondary metabolites in highly active fungal producers, in particular, increase the biosynthesis of β-lactams in the Penicillium chrysogenum Wis 54–1255 strain, an improved producer of penicillin G. In the current study, we demonstrate that the introduction of exogenous polyamines, such as spermidine or 1,3-diaminopropane, to A. chrysogenum wild-type (WT) and HY strains, leads to an increase in colony germination and morphological changes in a complete agar medium. The addition of 5 mM polyamines during fermentation increases the production of cephalosporin C in the A. chrysogenum HY strain by 15–20% and upregulates genes belonging to the beta-lactam biosynthetic cluster. The data obtained indicate the intersection of the metabolisms of polyamines and beta-lactams in A. chrysogenum and are important for the construction of improved producers of secondary metabolites in filamentous fungi.

Characterization of the Gene Encoding S-adenosyl-L-methionine (AdoMet) Synthetase in Penicillium chrysogenum; Role in Secondary Metabolism and Penicillin Production

“…This indicates that these compounds are also involved in controlling secondary metabolism in filamentous fungi. In fact, the intersection of the metabolisms of polyamines and β-lactams has also been recently confirmed in another β-lactam producer, Acremonium chrysogenum, where polyamines have been reported to upregulate cephalosporin C production and expression of β-lactam biosynthetic genes [47]. Interestingly, reduced levels of AdoMet also produced accumulation of a yellow-orange pigment.…”

Biotransformation of Androstenedione by Filamentous Fungi Isolated from Cultural Heritage Sites in the State Tretyakov Gallery

“…Over the past 60–70 years, improved strains of filamentous fungi have been widely used for the needs of medical biotechnology for the production of pharmaceutically significant secondary metabolites, such as antibiotics, statins, and immunosuppressants [ 46 , 47 , 48 , 49 ]. On the other hand, the use of filamentous fungi for a number of stages in the transformation of steroids for medicinal purposes has become widespread in biotechnology [ 1 , 16 ].…”

Penicillium chrysogenum, a Vintage Model with a Cutting-Edge Profile in Biotechnology

“…A similar LaeA-mediated effect of 1,3-diaminopropane and spermidine was also observed in the production of lovastatin by A. terreus [ 229 ]. In addition, CPC production in A. chrysogenum is likewise increased by these two polyamines concomitant with the upregulation of the biosynthetic genes [ 230 ]. Addition of 1,3-DAP or spermidine to P. chrysogenum cultures also stimulates the synthesis of enzymes involved in the biosynthesis of penicillin precursors [ 33 ].…”