On the contrary, roGFP1 expressed in the ER of P. pastoris wild-type cells was always fully oxidized, which is comparable to the results received for the ER of an S. cerevisiae wild-type strain with roGFP2 (Merksamer et al., 2008) and for the ER of mammalian cells with roGFP1 (Schwarzer et al., 2007). Based on the hypothesis that the midpoint potential of the compartment

has an influence on the functionality of the biosensor, we analyzed the P. pastoris wild-type strain with the constructs roGFP1_iE and roGFP1_iL, which theoretically have the optimal midpoint potential for the ER. Both of these constructs indicate a more oxidizing ER environment compared with the cytosol, but are not completely oxidized, as it was claimed when using roGFP1 and roGFP2 (Meyer et al., 2007; Schwarzer et al., 2007; Merksamer AZD6244 in vitro et al., 2008). The results obtained here appear to be more plausible than the redox ratios obtained with roGFP1. Comparing the redox ratios and the SDs determined with both variants, there is not much difference between roGFP1_iE and roGFP1_iL,

but according to the range of fluorescence between the oxidized and the reduced form of the protein, roGFP1_iE was chosen for further experiments. Determination of the thiol/disulfide equilibrium in different cell compartments has been of interest for years. Hwang et al. (1992) report that in CRL-1606 cells (murine B-lymphocytes), the reduction potential (E) for the redox pair GSSG/2GSH in the ER is −180 mV, while GSK126 molecular weight the cytosol has a value of −232 mV. Using the Nernst equation and the standard redox potential of the applied roGFP, the cellular reduction potential can be calculated based on the fluorescence data [Eqns (1)–(3)]. According to this calculation, the cytosol of P. pastoris has a reduction potential of −295 mV, which is in accordance with the results obtained

for S. cerevisiae (−289 mV; Ostergaard et al., 2004). As the ER is much more oxidizing, the reduction potential of this compartment should differ clearly from that of the cytosol. After targeting roGFP1 into the ER of the epithelial cell line CF15, the calculation Thiamine-diphosphate kinase of the reduction potential of this organelle seemed to be quite difficult, because the roGFP1 ratios were nearly saturated, indicating that the ER was more oxidized than −250 mV (Schwarzer et al., 2007). These data show similarities to the results of Merksamer et al. (2008) calculated for the S. cerevisiae ER when expressing roGFP2 in this compartment, but no reduction potentials were reported. This might be due to the fact that for fully oxidized redox sensors, the calculation yields no results. In the present study, the reduction potential of the ER was determined using the fluorescence data from the experiments with roGFP1_iE.

The majority of clones in sections 1 and 3 of the phylogenetic tree are likely to be specific to the concentrate diet as are those clones in sections 4–7 to the hay diet. The trend toward a closer phylogenetic relationship of clones retrieved from the specific dietary conditions implies the presence of diet-specific phylotypes of Prevotella. However, more direct evidence is needed in order to link the proposed diet-specific Prevotella lineages to their role in the ruminal fermentation of feed. Our DGGE data further showed a consistently higher number of bands in

samples from hay-fed animals. This finding corresponded with diversity analysis from clone libraries that showed higher diversity values (Chao1 and Shannon index) and a greater number of OTUs for clones generated from the hay diet. These results suggest the possible involvement of more AZD9291 datasheet diverse

members of Prevotella in the degradation of a hay diet than that of concentrate. Ceritinib mw In conclusion, Prevotella is a major member of the rumen bacterial community, and uncultured Prevotella constitute a large proportion of ruminal Prevotella. The diet-specific association of Prevotella clones observed suggests significant functional diversity of members of this genus in the rumen. This study provides evidence for the potential involvement of diverse groups of Prevotella in the degradation of feed in the rumen, particularly hay. “
“A group of bacterial strains formerly known as CDC group M-5 are opportunistic pathogens to humans. In 1993, a name, Neisseria weaveri, was proposed by two independent studies to harbor CDC group M-5 strains, namely N. weaveri Holmes et al. 1993 and N. weaveri Andersen et al. 1993, with two different ‘type’ strains. However, no study has been conducted on to the relatedness of the two ‘type’ strains,

although the close relationship of the two taxa has long been accepted unofficially. Niclosamide Formally, the status of the name N. weaveri Andersen et al. 1993 is illegitimate because it is a later homonym of N. weaveri Holmes et al., 1993; but the name of the strain is still validly published. In this study, we attempt to resolve the confusion caused by the apparent duplication of the species N. weaveri (with different type strains) using whole genome shotgun sequencing. We also sought to gain insight into the genetic characteristics of N. weaveri by conducting comparative genomics. On the basis of genomic similarities revealed through a comparative genomic study, we propose that N. weaveri Andersen et al. 1993 should be re-classified as a later heterotypic synonym of N. weaveri Holmes et al., 1993. The genus Neisseria is composed of commensal bacteria that colonize the mucus membranes of mammals. Neisseria encompasses two important pathogens – Neisseria meningitidis and Neisseria gonorrhoeae – as well as many other opportunistic pathogens (Janda & Knapp, 2003; Han et al., 2006).

, 2004). Carbon sources were used in 1% (w/v) final concentrations and are given at the respective results. Batch cultures were incubated on a rotary shaker (INFORS HT Multitron; 250 r.p.m.) at 30 °C in 500 mL Erlenmeyer flasks containing 100 mL of medium. Mycelia were pregrown in MM containing glycerol as a carbon source, harvested after 24 h by filtration on a sintered glass funnel, washed with cold sterile tap water and then transferred into fresh MM without glycerol, but supplemented with other carbon sources. For transcript analysis, samples were taken after 6 h of further incubation. Aspergillus niger conidiospores are not formed on d-galactose containing solid medium. As a consequence, except where

noted otherwise, we used glycerol as a sole carbon source to conidiate A. niger in the experiments aimed at investigating conidial stage events. Fungal mycelia or conidia were harvested by filtration, washed with distilled water, frozen Selleck Cobimetinib and ground under liquid nitrogen. For nucleic acid extraction, the Wizard Genomic DNA Purification Kit and SV Total RNA Isolation System (Promega) were used. Standard methods were used for electrophoresis, blotting Natural Product Library and hybridization of nucleic acids (Sambrook et al., 1989). Northern analysis was performed with the PCR DIG Probe Synthesis kit (Roche). An amount of RNA (5.5 μg) respectively, was loaded into each lane. Primers

for probe amplifications are given in Table 1. Mycelial dry mass was determined by withdrawing 2 × 5 mL aliquots from the culture, suction filtration through a preweighted glass wool filter and drying in an oven at 80 °C until constant weight. Data were averaged and deviated by not more than 14%. The concentration

of d-galactose in the growth medium was determined by HPLC analysis, using an H+ exchange column (Bio-Rad Aminex HPX-H+), employing 10 mM H2SO4 at 55 °C as mobile phase with isocratic elution and C59 a refractive index detection. To determinate the galactokinase activity, an HPLC method was used (Fekete et al., 2002). Specific galactokinase activities are reported as mg protein, which was determined by means of a modification of the method of Lowry (Peterson, 1983) using BSA for calibration. Mycelia were pregrown for 18 h on glycerol as a carbon source, harvested by gentle filtration and resuspended in 20 mL of carbon-free medium (MM) to give a final density of 1 mg mL−1. MM was inoculated with 106, 107 and 109 spores mL−1, respectively, when the d-galactose uptake of conidiospores were tested. After incubation at 30 °C for 60 min, 13.63 μL (0.2 mCi mL−1) of d-galactose-1-14C (G3143-14C; Sigma) was added to give 100 000–150 000 dpm mL−1 culture, and a further amount of cold d-galactose was added to give a final concentration of 1 mM. The cultures were incubated for further 6 h, and 1.0 mL of samples withdrawn in intervals of 30 or 60 min by immediately pipetting them into 1 mL of 1 M d-galactose and vigorous shaking.

, 2004). Carbon sources were used in 1% (w/v) final concentrations and are given at the respective results. Batch cultures were incubated on a rotary shaker (INFORS HT Multitron; 250 r.p.m.) at 30 °C in 500 mL Erlenmeyer flasks containing 100 mL of medium. Mycelia were pregrown in MM containing glycerol as a carbon source, harvested after 24 h by filtration on a sintered glass funnel, washed with cold sterile tap water and then transferred into fresh MM without glycerol, but supplemented with other carbon sources. For transcript analysis, samples were taken after 6 h of further incubation. Aspergillus niger conidiospores are not formed on d-galactose containing solid medium. As a consequence, except where

noted otherwise, we used glycerol as a sole carbon source to conidiate A. niger in the experiments aimed at investigating conidial stage events. Fungal mycelia or conidia were harvested by filtration, washed with distilled water, frozen selleck products and ground under liquid nitrogen. For nucleic acid extraction, the Wizard Genomic DNA Purification Kit and SV Total RNA Isolation System (Promega) were used. Standard methods were used for electrophoresis, blotting Bak protein and hybridization of nucleic acids (Sambrook et al., 1989). Northern analysis was performed with the PCR DIG Probe Synthesis kit (Roche). An amount of RNA (5.5 μg) respectively, was loaded into each lane. Primers

for probe amplifications are given in Table 1. Mycelial dry mass was determined by withdrawing 2 × 5 mL aliquots from the culture, suction filtration through a preweighted glass wool filter and drying in an oven at 80 °C until constant weight. Data were averaged and deviated by not more than 14%. The concentration

of d-galactose in the growth medium was determined by HPLC analysis, using an H+ exchange column (Bio-Rad Aminex HPX-H+), employing 10 mM H2SO4 at 55 °C as mobile phase with isocratic elution and Cell press a refractive index detection. To determinate the galactokinase activity, an HPLC method was used (Fekete et al., 2002). Specific galactokinase activities are reported as mg protein, which was determined by means of a modification of the method of Lowry (Peterson, 1983) using BSA for calibration. Mycelia were pregrown for 18 h on glycerol as a carbon source, harvested by gentle filtration and resuspended in 20 mL of carbon-free medium (MM) to give a final density of 1 mg mL−1. MM was inoculated with 106, 107 and 109 spores mL−1, respectively, when the d-galactose uptake of conidiospores were tested. After incubation at 30 °C for 60 min, 13.63 μL (0.2 mCi mL−1) of d-galactose-1-14C (G3143-14C; Sigma) was added to give 100 000–150 000 dpm mL−1 culture, and a further amount of cold d-galactose was added to give a final concentration of 1 mM. The cultures were incubated for further 6 h, and 1.0 mL of samples withdrawn in intervals of 30 or 60 min by immediately pipetting them into 1 mL of 1 M d-galactose and vigorous shaking.

Managing drug interactions (see above). Where the HIV drug has the potential to be adversely affected by another drug, and the combination is unavoidable, TDM may be used either to manage that interaction, or else discount a significant interaction in a particular patient.

Other situations. Knowledge of plasma–drug concentrations may be clinically useful when evaluating whether there is scope for treatment simplification, or else confirming or refuting impaired drug absorption Vorinostat as a reason for virological failure. More detailed recommendations for the use of TDM are available in the BHIVA guidelines for the routine investigation and monitoring of adult Ixazomib in vitro HIV-1-infected

individuals 2011 [52]. As for all other investigations, it is essential that TDM is undertaken correctly, especially with regard to timing (undertaken when steady state has been achieved). A consensus has been achieved for defining targets [53] for many ARVs. With many newer agents, evidence for a defined minimum target for efficacy is either weak or lacking, and evidence for an upper toxicity cut-off for most ARVs is lacking. We recommend patients stopping ART containing an NNRTI in combination with an NRTI backbone replace all drugs with a PI (LPV/r) for 4 weeks (1C). We recommend patients stopping a PI-containing regimen stop all drugs simultaneously and no replacement is required (1C). Proportion of patients with an undetectable VL on ART who, Sorafenib mouse on stopping a regimen containing an NNRTI in combination with a NRTI backbone,

are switched to PI/r for 4 weeks. In general, treatment interruptions are not recommended for most patients. Whatever the reason for stopping ART (e.g. drug toxicity, intercurrent illness, after pregnancy or patient choice), pharmacological issues must be considered for a clinician to give guidance. The half-life of each drug included in the regimen is critical. There is the potential for monotherapy or dual therapy if ARV drugs with different half-lives are stopped simultaneously. NNRTI and NRTI resistance mutations have been detected following discontinuation of previously suppressive regimens [54] and may have the potential to affect the likelihood of viral re-suppression on restarting an NNRTI-based ART regimen. There are limited data on which to base recommendations for how to protect against development of resistance in the period immediately following treatment cessation. Several discontinuation strategies have been proposed [55], and choice is influenced by clinical considerations, patient wishes and pharmacological principles.

, 2007). Selfing occurs under conditions favourable for sexual development, with closed fruiting bodies (cleistothecia), containing ascospores, being formed by all fertile strains (see Todd et al., 2007). Previously, we found that pex mutants, impaired in PTS1 protein import, were affected in sexual development, producing low numbers of small cleistothecia in selfings or homozygous crosses (Hynes et al., 2008). However, it was clear that meiosis was not blocked. We have RG7204 purchase now deleted the gene encoding Pex2 in order to test whether meiotic commitment is dependent on the RING-finger complex in A. nidulans. Unlike P. anserina, meiosis is not

affected, indicating a fundamental difference between these species. The media and conditions for growth of A. nidulans and standard genetic manipulations were as described previously (Todd et al., 2007). DNA from transformants was analysed by Southern blotting to confirm predicted integration events. Standard methods for DNA manipulations, nucleic acid Regorafenib ic50 blotting and hybridization have been described (Hynes et al., 2006). Unless otherwise indicated, strains contained the veA1 mutation.

This mutation results in increased conidiation and reduced sexual reproduction relative to veA+ strains (Kim et al., 2002). The isolation of the pexC∷bar and pexC∷bar; ve+ strains has been described (Hynes et al., 2008). A single gene encoding the homologue of Pex2 was identified as AN4056.3 in the A. nidulans genome database (http://www.broadinstitute.org/annotation/genome/aspergillus_group/MultiHome.html). A 2.7-kb fragment corresponding to coordinates −598 to +2098 (relative

to the predicted translation start) was amplified by the PCR using the primers 5′-AACATCCCCGCAAGATACAG-3′ and 5′-ATGAGTTCGAGAAGCGTCGT-3′ and inserted into EcoRV cut pBluescript SK+ to generate the plasmid pFK7442. A 2.1-kb XhoI–E coICRI fragment containing the Aspergillus fumigatus riboB gene (Nayak et al., 2006) was inserted between the XhoI and StuI sites of the insert of pFK7442 to generate pFK7447, thereby replacing sequences of AN4056 (+209 to +1177) corresponding to amino acids 71–379 (Fig. 1a). A Phospholipase D1 linear PCR fragment generated with the above primers was used to transform strain TNO2A21 (genotype pyroA4 nkuAΔ; veA1 riboB2) selecting for riboflavin prototrophy using standard methods (Nayak et al., 2006). The recipient strain contained the nkuAΔ to promote homologous integration events. blastp searches of the predicted proteins from the A. nidulans genome sequence with the P. anserina Pex2 sequence revealed a single homologue (AN4056.3) in agreement with the analysis of Kiel et al. (2006). The A. nidulans gene contains only one intron, while the predicted pex2 genes of other Aspergillus spp. contain two introns (Kiel et al., 2006). AN4056 was designated pexB in accordance with the standard nomenclature for A. nidulans.

Therefore, prescriptions should be in liquid form, that Selleckchem BIBW2992 is, soluble painkillers (analgesics), ideally a sugar-free form. Frequency of dental review should be scheduled according to the risk of caries every 3 to 6 months5,15,22,27. As the predisposition to develop intraoral carcinoma (SSC) increases with age, cancer screening must be considered a very important aspect of the review appointment in patients with RDEB from the second decade on19,28. Routine dental treatment can be provided5,22,29.

Dental management does not require many modifications4; however, a careful approach is advised as tissue manipulation can produce oral ulceration. This group of patients requires an aggressive preventive programme and frequent visits to the dentist as they present enamel hypoplasia/defects, leading to an increased risk for cavities and severe attrition. Patients with DDEB are able to receive routine dental treatment with little or no modifications28. Patients with the severe generalized RDEB subtype of EB require several treatment modifications and a careful approach to avoid as much tissue damage as possible. Management of Tanespimycin these patients ideally requires a well-organized multidisciplinary team approach27,30 with good communication involving case discussion. 1 Lubrication Lips should always be lubricated with Vaseline®/petrolatum or other appropriate lubricant before any procedure is performed to reduce

adherence and lesions formation1,5,18,27,31. Bullae formation or epithelium sloughing can occur upon contact with the suction tip1. It is suggested to lean the

suction tip or saliva ejector upon hard tissue, that is, on the tooth surface. High vacuum suction should be avoided. Blood- or fluid-filled bullae that occur during treatment have to be drained with a sterile needle or by a cut with scissors to avoid lesion expansion because of fluid pressure13,22,23,33. Extreme care of fragile tissues is important. To handle tissues, a little pressure (compressive forces) can be applied, but no sliding movements (lateral traction or other shear forces) should MG-132 mw be used, as these can cause tissue sloughing5,11,23. At the end of every clinical session, it is important to check for fluid-filled blisters and drain them. It is also important to check whether there are remnants of dental materials. A careful approach is advised, as mucosal sloughing can form following dental treatment34. In patients with severe generalized RDEB, periapical technique is difficult in the posterior area because of microstomia, ankyloglossia, and scarring of the sublingual area. Orthopantomography (panoramic) is the investigation of choice. Other alternatives are as follows: small films bitewings, extraoral bitewings capabilities in panoramic radiographs (if equipment is available), and occlusal or lateral oblique techniques. There are no contraindications to the use of conventional dental materials5,38.

Design.  Data were collected from 1057 children; validated questionnaires were completed, Erastin concentration and children were examined by trained dentist at ages 3 and 5. Logistic regression analyses were performed to explain dental attendance. Results.  At the age of 3, 62% and by 5 years, 21% had never visited the dentist. The first dental visit was considered a pleasant experience for the majority of children. Multivariable regression analyses revealed that children who were not first born, whose mothers had a higher educational level and whose parents had recently visited the

dentist, had significantly higher odds for having visited the dentist at young age. Conclusions.  Parents of young children need to be informed about and motivated for an early dental visit. Promotion campaigns should focus on firstborn children, children

from less educated parents, and parents who do not regularly see a dentist. “
“A wide range for the prevalence of Molar–Incisor–Hypomineralisation (MIH) has been found in regional studies. The aim of this click here study was to determine the prevalence of MIH in Germany and to compare the findings with other studies. In the compulsory dental school examination, the first permanent molars, permanent incisors, and second primary molars were examined according to EAPD criteria in 2395 children (8.1 ± 0.8 years) in four regions in Germany for the presence of MIH. Examinations were performed by five calibrated examiners (κ = 0.9) on clean teeth after toothbrushing. The prevalence of MIH at the four regions differed considerably (4.3–14.6%) with a mean prevalence of 10.1%. The

selleck screening library DMFT/dmft was generally low, but children with MIH exhibited statistically significant higher caries values. A total of 12.0% of the children with MIH also had at least one affected primary molar, which resulted in a statistically significant correlation between primary and permanent teeth. Most of the affected teeth had demarcated opacities, but more than half of the affected children showed at least one tooth with severe MIH. Molar–Incisor–Hypomineralisation is a prevalent finding in German school children. The prevalence varies highly in different regions, and the high rate of severe forms has clinically relevant implications. “
“International Journal of Paediatric Dentistry 2010; 20: 158–164 Background.  Caries is a disease that affects both primary and permanent dentitions, therefore new methods of caries diagnosis need to be tested on primary teeth as well as on permanent teeth. Aim.  This study reports the application of optical coherence tomography (OCT) to characterize sound dental structure and detect natural caries of human primary teeth. Design.  Six primary teeth were sectioned into thin slices (∼1.5 mm), and analysed perpendicular to the enamel surface by two home-made OCT systems operating around 1280 and 840 nm. The generated images were compared with histology as the gold standard. Results.

Notably, Yamada and colleagues used the system for both random integration of T-

(transferred) DNA and targeted insertion, for example disruption of the areA/nit-2 gene. As another alternative transformation technique, electroporation of germinated conidia was applied in T. rubrum, allowing the random integration of hph and eGFP (Dobrowolska & Staczek, 2009). Although not many comparative data on Thiazovivin clinical trial transformation efficiency are available – some species have not even been addressed at all – different dermatophyte species appear to be more or less amenable to DNA uptake and/or stable integration. Therefore, transformation protocols established for a selected species are not necessarily transferable to another, but require precise modifications. From our own work, we know for example that our standard PEG-protocol for the efficient transformation of A. benhamiae was not directly applicable for T. rubrum or M. canis.

The reasons for this observation are likely multifactorial, http://www.selleckchem.com/products/ABT-263.html including differential protoplast stability, cell wall composition, microconidia production, etc. Filamentous fungi are known to only poorly support site-directed insertion of linear DNA cassettes in the genome by homologous recombination, in contrast to yeasts such as Saccharomyces cerevisiae or the opportunistic pathogen C. albicans. Therefore, in filamentous fungi, identification of transformants with a desired genetic alteration has proven laborious in many cases. In order to circumvent this obstacle, parental strains were generated in diverse species that lack the nonhomologous end joining (NHEJ) recombination pathway, for example in N. crassa (Ninomiya et al., 2004), Aspergillus

spp. (da Silva Ferreira et al., 2006; Krappmann et al., 2006; Nayak et al., 2006), and since recently, also in T. mentagrophytes (Yamada et al., 2009a) and A. benhamiae Cobimetinib molecular weight (Grumbt et al., 2011) (Table 1). Mutants deficient in NHEJ processes allow a strongly increased frequency of targeted insertions; however, an altered risk of unforeseen genetic variations cannot be excluded. In dermatophyte species, only a small number of genes have so far been analysed by targeted inactivation, for example pacC and MDR2 in T. rubrum (Fachin et al., 2006; Ferreira-Nozawa et al., 2006), Ku80, areA and Trim4 in T. mentagrophytes (Yamada et al., 2009a, b), areA in M. canis (Yamada et al., 2006) and Ku70 and AcuE in A. benhamiae (Grumbt et al., 2011). Interestingly, A. benhamiae has been shown in our work to allow efficient targeted gene deletion not only in a ku70 mutant background but also in the wild-type strain. This has been demonstrated by the construction of mutants in malate synthase AcuE, KU70 and other candidates (Grumbt et al., 2011; M. Grumbt and P. Staib, unpublished data). The use of two different dominant selection markers, hph and neo, even allowed for the first time the site-directed complementation of knockout mutant strains. Because the deletion of KU70 had no adverse effect on the virulence of A.

spinosa trans1

compared with 100 (± 7.7) mg L−1 in the parental strain. Quantitative real time polymerase chain reaction analysis of three selected genes (spnH, spnI, and spnK) confirmed the positive effect of the overexpression of these genes on the spinosyn production. This study provides a simple avenue for enhancing spinosyn Copanlisib production. The strategies could also be used to improve the yield of other secondary metabolites. Saccharopolyspora spinosa was originally isolated in 1982 from a soil sample collected in a Caribbean island (Mertz & Yao, 1990). Fermentation broth extracts from this strain contain a series of spinosyn factors that are highly efficient against a broad range of pests, and appear to INCB018424 manufacturer have little or no effect on non-target insects and mammals (Sparks et al., 1998). Previous studies showed that spinosyns are derived from nine acetate and two propionate units, which produce a cyclized polyketide molecule; three carbon–carbon bonds are soon formed to obtain the tetracyclic aglycone (AGL). The rhamnose is subsequently attached and is tri-O-methylated to yield the intermediate pseudoaglycone (PSA), followed by the incorporation of forosamine sugar, giving the final spinosyns product. The most active and abundant spinosyns from S. spinosa fermentation broth are spinosyn A and spinosyn D. They differ from each

other by a single methyl substituent at position 6 of the polyketide. Other factors of the spinosyn family, produced as minor components, exhibit different methylation patterns and are significantly less active (Crouse et al., 2001). A naturally occurring mixture of spinosyn A (c. 85% of spinosad) and spinosyn D (c. 15%

of spinosad) is called spinosad (Waldron et al., 2001). The c. 74-kb spinosyn biosynthetic Thalidomide gene cluster contains 23 open reading frames (ORF) including five genes encoding a type I polyketide synthase (PKS) (spnA, B, C, D, and E); four genes involved in intramolecular C–C bond formation (spnF, J, L, and M); four genes responsible for rhamnose attachment and methylation (spnG, I, K, and H); six genes participating in forosamine biosynthesis (spnP, O, N, Q, R, and S) and four genes (ORF-L15, ORF-L16, ORF-R1, and ORF-R2) with no proven role in spinosyn biosynthesis (Waldron et al., 2001). The genes involved in rhamnose biosynthesis (gtt, gdh, epi, and kre) are not linked to this cluster (Madduri et al., 2001b). Traditionally, improvement of secondary metabolite-producing strains is achieved by random mutagenesis and selection techniques (Parekh et al., 2000). Although these techniques have succeeded in generating many industrial strains, they are time-consuming and costly. Rational strain improvement strategies overlap with classical approaches in generating a mutant population (Adrio & Demain, 2006).