scholarly journals ANTIBIOTIC BIOSYNTHESIS AND SECONDARY METABOLISM IN HIGH-YIELDING STRAINS OF STREPTOMYCES, PENICILLIUM CHRYSOGENUM AND ACREMONIUM CHRYSOGENUM

2019 ◽  
Vol 56 (4) ◽  
pp. 422-428
Author(s):  
Wiesław Kurzątkowski ◽  
Joanna Kuczerowska
2016 ◽  
Vol 82 (20) ◽  
pp. 6247-6257 ◽  
Author(s):  
Christian Derntl ◽  
Alice Rassinger ◽  
Ewald Srebotnik ◽  
Robert L. Mach ◽  
Astrid R. Mach-Aigner

ABSTRACTThe industrially used ascomyceteTrichoderma reeseisecretes a typical yellow pigment during cultivation, while otherTrichodermaspecies do not. A comparative genomic analysis suggested that a putative secondary metabolism cluster, containing two polyketide-synthase encoding genes, is responsible for the yellow pigment synthesis. This cluster is conserved in a set of rather distantly related fungi, includingAcremonium chrysogenumandPenicillium chrysogenum. In an attempt to silence the cluster inT. reesei, two genes of the cluster encoding transcription factors were individually deleted. For a complete genetic proof-of-function, the genes were reinserted into the genomes of the respective deletion strains. The deletion of the first transcription factor (termed yellow pigment regulator 1 [Ypr1]) resulted in the full abolishment of the yellow pigment formation and the expression of most genes of this cluster. A comparative high-pressure liquid chromatography (HPLC) analysis of supernatants of theypr1deletion and its parent strain suggested the presence of several yellow compounds inT. reeseithat are all derived from the same cluster. A subsequent gas chromatography/mass spectrometry analysis strongly indicated the presence of sorbicillin in the major HPLC peak. The presence of the second transcription factor, termed yellow pigment regulator 2 (Ypr2), reduces the yellow pigment formation and the expression of most cluster genes, including the gene encoding the activator Ypr1.IMPORTANCETrichoderma reeseiis used for industry-scale production of carbohydrate-active enzymes. During growth, it secretes a typical yellow pigment. This is not favorable for industrial enzyme production because it makes the downstream process more complicated and thus increases operating costs. In this study, we demonstrate which regulators influence the synthesis of the yellow pigment. Based on these data, we also provide indication as to which genes are under the control of these regulators and are finally responsible for the biosynthesis of the yellow pigment. These genes are organized in a cluster that is also found in other industrially relevant fungi, such as the two antibiotic producersPenicillium chrysogenumandAcremonium chrysogenum. The targeted manipulation of a secondary metabolism cluster is an important option for any biotechnologically applied microorganism.


Microbiology ◽  
2003 ◽  
Vol 149 (8) ◽  
pp. 1991-2004 ◽  
Author(s):  
Liru Wang ◽  
Leo C. Vining

Three new genes (jadW 1, jadW 2 and jadW 3) were isolated from a region of the Streptomyces venezuelae ISP5230 chromosome at the left-hand end of the jad cluster for jadomycin B (JdB) biosynthesis. The deduced amino acid sequence of jadW 1 showed strong similarity to gene products associated in several streptomycetes with γ-butyrolactone autoregulators controlling morphological differentiation and secondary metabolism. Examination of JadW1 for conserved domains detected a repeat sequence characteristic of proteins in the AfsA regulatory family. Insertional inactivation of jadW 1 reduced the growth rate of S. venezuelae cultures in aerated liquid media containing complex nitrogen sources and altered growth morphology in minimal medium. It also affected sporulation on agar media. Cultures of jadW 1-disrupted mutants grown under conditions supporting biosynthesis of JdB or chloramphenicol by the wild-type strain failed to produce either of the antibiotics. Complementing the disrupted strain by transformation with pJV435, containing a cloned copy of the gene, improved sporulation and restored antibiotic biosynthesis in transformants to titres close to those of the wild-type similarly transformed with pJV435 as a control. The results are consistent with a role for jadW 1 in regulating morphological and metabolic differentiation. Further sequence analysis of jadR 2, which functions with jadR 1 in stress-induced activation of JdB biosynthesis, indicated that this gene encodes a γ-butyrolactone receptor homologue. The growth-rate-sensitive phenotype of the jadW 1-disrupted mutant, and the proximity of jadW 1 to jadR 2 indicate that this region of the jad gene cluster contains a regulatory mechanism incorporating γ-butyrolactone signalling and sensitivity to environmental stress.


1986 ◽  
Vol 4 (1) ◽  
pp. 44-47 ◽  
Author(s):  
J. M. Luengo ◽  
M. T. Alemany ◽  
F. Salto ◽  
F. Ramos ◽  
M. J. López-Nieto ◽  
...  

2018 ◽  
Author(s):  
Ghader Bashiri ◽  
James Antoney ◽  
Ehab N. M. Jirgis ◽  
Mihir V. Shah ◽  
Blair Ney ◽  
...  

AbstractCofactor F420plays critical roles in primary and secondary metabolism in a range of bacteria and archaea as a low-potential hydride transfer agent. It mediates a variety of important redox transformations involved in bacterial persistence, antibiotic biosynthesis, pro-drug activation and methanogenesis. However, the biosynthetic pathway for F420has not been fully eluci-dated: neither the enzyme that generates the putative intermediate 2-phospho-L-lactate, nor the function of the FMN-binding C-terminal domain of the γ-glutamyl ligase (FbiB) in bacteria are known. Here we show that the guanylyltransferases FbiD and CofC accept phosphoenolpyruvate, rather than 2-phospho-L-lactate, as their substrate, leading to the formation of the previously uncharacterized intermediate, dehydro-F420-0. The C-terminal domain of FbiB then utilizes FMNH2 to reduce dehydro-F420-0, which produces mature F420species when combined with the γ-glutamyl ligase activity of the N-terminal domain. This new insight has allowed the heterologous expression F420from a recombinant F420biosynthetic pathway inEscherichia coli.


2008 ◽  
Vol 75 (2) ◽  
pp. 209-218 ◽  
Author(s):  
Ricardo V. Ullán ◽  
Ramiro P. Godio ◽  
Fernando Teijeira ◽  
Inmaculada Vaca ◽  
Carlos García-Estrada ◽  
...  

mBio ◽  
2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Qing Yan ◽  
Lucas D. Lopes ◽  
Brenda T. Shaffer ◽  
Teresa A. Kidarsa ◽  
Oliver Vining ◽  
...  

ABSTRACTSecondary metabolites are synthesized by many microorganisms and provide a fitness benefit in the presence of competitors and predators. Secondary metabolism also can be costly, as it shunts energy and intermediates from primary metabolism. InPseudomonasspp., secondary metabolism is controlled by the GacS-GacA global regulatory system. Intriguingly, spontaneous mutations ingacSorgacA(Gac−mutants) are commonly observed in laboratory cultures. Here we investigated the role of secondary metabolism in the accumulation of Gac−mutants inPseudomonas protegensstrain Pf-5. Our results showed that secondary metabolism, specifically biosynthesis of the antimicrobial compound pyoluteorin, contributes significantly to the accumulation of Gac−mutants. Pyoluteorin biosynthesis, which poses a metabolic burden on the producer cells, but not pyoluteorin itself, leads to the accumulation of the spontaneous mutants. Interspecific competition also influenced the accumulation of the Gac−mutants: a reduced proportion of Gac−mutants accumulated whenP. protegensPf-5 was cocultured withBacillus subtilisthan in pure cultures of strain Pf-5. Overall, our study associated a fitness trade-off with secondary metabolism, with metabolic costs versus competitive benefits of production influencing the evolution ofP. protegens, assessed by the accumulation of Gac−mutants.IMPORTANCEMany microorganisms produce antibiotics, which contribute to ecologic fitness in natural environments where microbes constantly compete for resources with other organisms. However, biosynthesis of antibiotics is costly due to the metabolic burdens of the antibiotic-producing microorganism. Our results provide an example of the fitness trade-off associated with antibiotic production. Under noncompetitive conditions, antibiotic biosynthesis led to accumulation of spontaneous mutants lacking a master regulator of antibiotic production. However, relatively few of these spontaneous mutants accumulated when a competitor was present. Results from this work provide information on the evolution of antibiotic biosynthesis and provide a framework for their discovery and regulation.


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