could be found among alkaliphiles. Other possible targets can be cell wall and
synthesis of specific lipids found in alkaliphiles.
There are relatively many publications on isolation of antimicrobial compounds
from various classes of alkaliphiles. The majority of the studies have only dealt with
detection of the antimicrobial activity but not the analysis of the product structures or
the mechanism of action. Seemingly, there is not so much practical value finding the
same molecular structure from an alkaliphile which is already known from other
sources and probably studied already including its production. However, there
remains a probability that the main antibiotic components are synthetized with a
set of different isomers, and it appears that one or more of the isomers are more
active and/or more specific than the known drug. A well-known example is the
fungal antibiotic cyclosporine, having many structural isomers (A, B, C, D) with a
set of biological activities. The isomer spectrum is commonly specific to the
producer strain. The antibiotics are often produced with special multienzyme complexes giving rise to a great number of variations of the products. Less accurate
specificities of the enzymes in the complex add to the variation. The origin of the
generation of the isomeric structures by the microbes may have the purpose of
offering a wider-spectrum antibiotic. In spite of the possibility of finding new
isomers from alkaliphiles, the most desirable target is a new antibiotic having the
above-described innovative features (WHO/EMP/IAU/2017.11).
The methods for screening of antibiotics from alkaliphiles are often straightforward. Antibiotics are generally more or less hydrophobic. After cultivation, growth
medium with or without cells are subjected to two-phase extraction or treated with
hydrophobic polymers. Another way is to dry the medium and extract with organic
solvents. After evaporation of the solvent, and redissolving in an aqueous phase,
extracts can be used for preliminary testing the antimicrobial activities on Petri
dishes inoculated with an indicator microbe. The raw extracts with antimicrobial
activities are then studied further with chromatographic fractioning, and finally, the
structures are determined with NMR, HPLC-MS, and other spectroscopic methods.
A typical isolation and identification process for antifungal cyclic lipopeptides from
a neutral-growing Paenibacillus sp. is described by Aktuganov et al. [95].
Most of the antibiotics from non-extreme terrestrial microorganisms are originated from actinomycetes. The genus Streptomyces is the well-known source of
naturally occurring antimicrobial substances [96]. In recent years, the rate of discovery of novel compounds from microorganisms thriving in moderate environment
has decreased, and repeated appearance of the same compounds has made them less
attractive for screening programs [97]. Currently, research efforts have focused on
microbes living in extreme habitats. Great taxonomical variety of alkaliphilic and
moderately haloalkaliphilic bacterial isolates exhibiting antimicrobial activities were
obtained from Lonar Lake, India [98–100]. Haloalkaliphilic actinomycetes such as
Nocardiopsis sp. and Streptomyces sp. from the mud soil of solar salt works in India,
in vitro, had effectively suppressed the growth of most of the pathogenic bacteria, as
well as pathogenic fungi [101]. The haloalkaliphilic and alkaliphilic actinomycetes
from saline desert of Kutch, India, produced the antimicrobial compounds against
Gram-positive and Gram-negative bacteria [102, 103]. Alkaliphilic fungi which can
Metabolites Produced by Alkaliphiles with Potential Biotechnological. . .
181
synthesis of specific lipids found in alkaliphiles.
There are relatively many publications on isolation of antimicrobial compounds
from various classes of alkaliphiles. The majority of the studies have only dealt with
detection of the antimicrobial activity but not the analysis of the product structures or
the mechanism of action. Seemingly, there is not so much practical value finding the
same molecular structure from an alkaliphile which is already known from other
sources and probably studied already including its production. However, there
remains a probability that the main antibiotic components are synthetized with a
set of different isomers, and it appears that one or more of the isomers are more
active and/or more specific than the known drug. A well-known example is the
fungal antibiotic cyclosporine, having many structural isomers (A, B, C, D) with a
set of biological activities. The isomer spectrum is commonly specific to the
producer strain. The antibiotics are often produced with special multienzyme complexes giving rise to a great number of variations of the products. Less accurate
specificities of the enzymes in the complex add to the variation. The origin of the
generation of the isomeric structures by the microbes may have the purpose of
offering a wider-spectrum antibiotic. In spite of the possibility of finding new
isomers from alkaliphiles, the most desirable target is a new antibiotic having the
above-described innovative features (WHO/EMP/IAU/2017.11).
The methods for screening of antibiotics from alkaliphiles are often straightforward. Antibiotics are generally more or less hydrophobic. After cultivation, growth
medium with or without cells are subjected to two-phase extraction or treated with
hydrophobic polymers. Another way is to dry the medium and extract with organic
solvents. After evaporation of the solvent, and redissolving in an aqueous phase,
extracts can be used for preliminary testing the antimicrobial activities on Petri
dishes inoculated with an indicator microbe. The raw extracts with antimicrobial
activities are then studied further with chromatographic fractioning, and finally, the
structures are determined with NMR, HPLC-MS, and other spectroscopic methods.
A typical isolation and identification process for antifungal cyclic lipopeptides from
a neutral-growing Paenibacillus sp. is described by Aktuganov et al. [95].
Most of the antibiotics from non-extreme terrestrial microorganisms are originated from actinomycetes. The genus Streptomyces is the well-known source of
naturally occurring antimicrobial substances [96]. In recent years, the rate of discovery of novel compounds from microorganisms thriving in moderate environment
has decreased, and repeated appearance of the same compounds has made them less
attractive for screening programs [97]. Currently, research efforts have focused on
microbes living in extreme habitats. Great taxonomical variety of alkaliphilic and
moderately haloalkaliphilic bacterial isolates exhibiting antimicrobial activities were
obtained from Lonar Lake, India [98–100]. Haloalkaliphilic actinomycetes such as
Nocardiopsis sp. and Streptomyces sp. from the mud soil of solar salt works in India,
in vitro, had effectively suppressed the growth of most of the pathogenic bacteria, as
well as pathogenic fungi [101]. The haloalkaliphilic and alkaliphilic actinomycetes
from saline desert of Kutch, India, produced the antimicrobial compounds against
Gram-positive and Gram-negative bacteria [102, 103]. Alkaliphilic fungi which can
Metabolites Produced by Alkaliphiles with Potential Biotechnological. . .
181