METABOLIC PATHWAYS FOR BIOSYNTHESIS OF INDUSTRIAL MICROBIOLOGY PRODUCTS CONTD..
From studies on Penicillium urticae the terms trophophase and idiophase were introduced
to distinguish the two phases in the growth of organisms producing secondary
metabolites. The trophophase (Greek, tropho = nutrient) is the feeding phase during
which primary metabolism occurs. In a batch culture this would be in the logarithmic
phase of the growth curve. Following the trophophase is the idio-phase (Greek, idio = peculiar) during which secondary metabolites peculiar to, or characteristic of, a given organism are synthesized.
Secondary synthesis occurs in the late logarithmic, and in the
stationary, phase. It has been suggested that secondary metabolites be described as 'idiolites' to distinguish them from primary metabolites.
ROLE OF SECONDARY METABOLITES IN THE PHYSIOLOGY OF ORGANISMS PRODUCING THEM:
Since many industrial microbiological products result from secondary metabolism,
workers have sought to explain the role of secondary metabolites in the survival of the
organism. Due to the importance of antibiotics as clinical tools, the focus of many workers
has been on antibiotics. This discussion while including antibiotics will attempt to
embrace the whole area of secondary metabolites.
Some earlier hypotheses for the existence of secondary metabolism are apparently no
longer considered acceptable by workers in the field. These include the hypotheses that
secondary metabolites are food-storage materials, that they are waste products of the
metabolism of the cell and that they are breakdown products from macro-molecules. The
theories in currency are discussed below; even then none of these can be said to be water
tight. The rationale for examining them is that a better understanding of the organism’s physiology will help towards manipulating it more rationally for maximum productivity.
(i) The competition hypothesis: In this theory which refers to antibiotics specifically,
secondary metabolites (antibiotics) enable the producing organism to withstand
competition for food from other soil organisms. In support of this hypothesis is the
fact that antibiotic production can be demonstrated in sterile and non-sterile soil,
which may or may not have been supplemented with organic materials. As further
support for this theory, it is claimed that the wide distribution of Beta-lactamases
among microorganisms is to help these organisms detoxify the Beta-lactam
antibiotics. The obvious limitation of this theory is that it is restricted to antibiotics
and that many antibiotics exist outside Beta-lactams.
(ii) The maintenance hypothesis: Secondary metabolism usually occurs with the
exhaustion of a vital nutrient such as glucose. It is therefore claimed that the
selective advantage of secondary metabolism is that it serves to maintain
mechanisms essential to cell multiplication in operative order when that cell
multiplication is no longer possible. Thus by forming secondary enzymes, the
enzymes of primary metabolism which produce precursors for secondary
metabolism therefore, the enzymes of primary metabolism would be destroyed. In
this hypothesis therefore, the secondary metabolite itself is not important; what is
important is the pathway of producing it.
(iii) The unbalanced growth hypothesis: Similar to the maintenance theory, this
hypothesis states that control mechanisms in some organisms are too weak to
prevent the over synthesis of some primary metabolites. These primary metabolites
are converted into secondary metabolites that are excreted from the cell. If they are
not so converted they would lead to the death of the organism.
(iv) The detoxification hypothesis: This hypothesis states that molecules accumulated
in the cell are detoxified to yield antibiotics. This is consistent with the observation
that the penicillin precursor penicillanic acid is more toxic to Penicillium chrysogenum
than benzyl penicillin. Nevertheless not many toxic precursors of
antibiotics have been observed.
(v) The regulatory hypothesis: Secondary metabolite production is known to be
associated with morphological differentiation in producing organisms. In the fungus Neurospora crassa, carotenoids are produced during sporulation. In
Cephalospoium acremonium, cephalosporin C is produced during the idiophase
when arthrospores are produced. Numerous examples of the release of secondary
metabolites with some morphological differentiation have been observed in fungi.
One of the most intriguing relationships between differentiation and secondary
metabolite production, is that between the production of peptide antibiotics by
Bacillus spp. and spore formation. Both spore formation and antibiotic production
are suppressed by glucose; non-spore forming mutants of bacilli also do not
produce antibiotics, while reversion to spore formation is accompanied by
antibiotic formation has been observed in actinomycetes. Many roles have been
assigned to antibiotics in spore formers but the most clearly demonstrated has been
the essential nature of gramicidin in sporulation of Bacillus spp. The absence of the
antibiotic leads to partial deficiencies in the formation of enzymes involved in
spore formation, resulting in abnormally heat-sensitive spores. Peptide antibiotics
therefore suppress the vegetative genes allowing proper development of the
spores. In this theory therefore the production of secondary metabolites is
necessary to regulate some morphological changes in the organism. It could of
course be that some external mechanism triggers off secondary metabolite
production as well as the morphological change.
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CITED BY KAMAL SINGH KHADKA
Msc Microbiology, TU.
Assistant Professor in Pokhara University, Pokhara Bigyan Thata Prabidhi Campus, PNC, LA, NA.