Effect of ammonium in medium on ansamitocin P-3 production by Actinosynnema pretiosum

Abstract

Ansamitocin P-3 (AP-3) is an antitumor agent produced by ^ÅíáåçëóååÉã~=éêÉíáçëìã with a market demand for large and cheap supply, but its productivity is yet low. This work investigated the effects of ammonium in medium on the productivity, enzyme activities, and gene transcription for AP-3 biosynthesis. As observed, AP-3 production was depressed by medium ammonium, although the dry cell weight and the consumption of total sugar and isobutanol were not influenced obviously. From the onset of AP-3 accumulation, isobutyrate accumulation showed a different behavior in medium with or without ammonium. Isobutanol dehydrogenase activity was enhanced during production phase in medium with ammonium, but valine dehydrogenase activity was not substantially changed. qRT-PCR analysis revealed that transcriptional levels of structure genes=~ëãNQI ~ëãOQI ~ëãQP, and ~ëãNV were down-regulated by medium ammonium. The transcription of regulatory gene ~ëãO,=~ëãOVI=and=~ëãPN were slightly up-regulated while that of ~ëãPV was down-regulated by ammonium. The results indicated that inhibition of AP-3 production by ammonium might be related to the AP-3 ester side chain supply and the repression of gene transcription responsible for 3-amino-5-hydroxybenzoic acid and methoxymalonyl-ACP biosynthesis. The information is useful for future AP-3 productivity enhancement. © KSBB hÉóïçêÇëW=^åë~ãáíçÅáå=mJPI=ãÉÇáìã=~ããçåáìã=ÉÑÑÉÅíI=ÖÉåÉ=íê~åëÅêáéíáçåI=ÉåòóãÉ=~Åíáîáíó= = = = =

Process optimization with alternative carbon sources and modulation of secondary metabolism for enhanced ansamitocin P-3 production in Actinosynnema pretiosum

“…Glucose used as major carbon source was reported in several literatures for AP-3 production in A. pretiosum (Jia and Zhong, 2011;Lin et al, 2010Lin et al, , 2011. The repression effect of glucose might limit the potential yield of AP-3.…”

“…Approaches such as genetic modification (Bandi et al, 2006;Ng et al, 2009) and medium optimization (Bandi et al, 2006;Gao et al, 2014;Jia and Zhong, 2011;Lin et al, 2010Lin et al, , 2011Srinivasulu et al, 2005) have been developed for the improvement of AP-3 production; however, the resulting titers do not meet the requirement of industrial production. Efficient manipulation of fermentation process is therefore still essential to enhance both the yield and productivity of AP-3.…”

Improved Bioactive Metabolite Production by Saccharopolyspora halotolerans VSM-2 Using Response Surface Methodology and Unstructured Kinetic Modelling

“…Several environmental factors including temperature, pH and incubation period greatly influence the metabolite production in addition to carbon and nitrogen source. 7 Response Surface methodology (RSM) is a competent statistical method for model development and optimization of the complex process variables for the bioactive metabolite production due to its efficiency and experimental interpretation. 8 The key features of the RSM application are the reduced number of the experiments accompanied with the process variables interaction effects.…”

Optimization of Medium Composition for Antibacterial Metabolite Production From Streptomyces Sp.

“…Production of secondary metabolites through fermentation is influenced by various environmental factors, including nutrients nitrogen, phosphorus, and carbon sources [11][12][13]. Furthermore, production of valuable metabolites by Streptomyces differs qualitatively and quantitatively depending on the strains used in fermentation as one of the most significantroles as sources of precursors and energies for secondary metabolite production [14].…”