Table 2.
Summary of different biotechnological approaches for secondary metabolite production by Streptomyces
| Streptomyces strain | Secondary metabolite | Nutrients and metabolism | Fermentation medium (*1.0 L) | Growth conditions | Production (g·L-1) | Productivity (g·L-1 ·h-1) | Reference |
| S. griseus | Streptomycin | Optimization of pH, carbon source, and metal ions | 10.0 g Slb St, 0.3 g casein, 2.0 g K2HPO4, 2.0 g KNO3, 2.0 g NaCl, 0.2 g CaCO3, 0.01 g FeSO4, 0.05 g MgSO4·7H2O | Agar plates, 37 °C, pH = 8.5, 96 h | 4.30 | 0.045 | Singh et al. 2014 |
| S. kathirae SC-1 | Melanin | Optimization of carbon source, nitrogen source, and metal ions by response surface method | 3.27 g Amylo Dext, 37.0 g YE, 5.0 g NaCl, 0.1 g CaCl2, 50 μmol CuSO4, 0.25 mg tyrosine | Shake flask, 28 °C, pH = 6.0, 200 rpm, 128 h | 13.7 | 0.107 | Guo et al. 2014 |
| S. coelicolor A3(2) M145 | Actinorhodin and undecylprodigiosin | Optimization of phosphate and l-glutamate concentrations in the media, optimization of agitation speed and DO percentage | 55.2 g sodium-glutamate, 40.0 g Glc, 2 mmol MgSO4, 4.6 mmol phosphate, 0.028 g FeSO4∙7 H2O, 0.002 g CuSO4∙5 H2O, 0.0024 g ZnSO4∙7 H2O, 0.008 g MnSO4∙H2O, 5.6∙10−5 g Na2MoO4∙2 H2O, 11.2∙10−5 g CoCl2∙6 H2O | 3.0-L fermentor, 30 °C, pH = 7.0, 0.3–0.5 vvm, 900–1300 rpm, 70 h | - | 0.013 and 0.033 (sp. units·gcdw-1∙h-1) | Wentzel et al. 2012 |
| S. roseosporus NRRL11379 | Daptomycin | Supplementation with sodium decanoate as antibiotic precursor and optimized fed-batch feeding with dextrose | 11.0 g YE, 0.86 g Fe(NH4)2SO4·6H2O, 10.7 g dextrose, 72.0 g potato Dext, 7.2 g cane molasses | 3.6-L fermentor, 30 °C, pH = 6.5, 3.5 vvm, 450 rpm, 288 h | 0.81 | 0.003 | Ng et al. 2014 |
| Streptomyces strain | Secondary metabolite | Fermentation strategies | Fermentation medium (*1.0 L) | Growth conditions | Production (g·L-1) | Productivity (g·L-1· h-1) | Reference |
| S. cyaneogrisueus ssp. noncyanogenus | Nemadectin | WHd + RT impeller configuration, 25–55% DO by O2 supply, moderate agitation speed | 20.0 g Glc, 90.0 g CS, 25.0 g SoyF, 5.0 g YE, 4.0 g CaCO3,11.0 g MgSO4·7H2O, 0.01 g CuSO4, 0.002 g CoCl2, 0.001 g MnSO4 | 5.0-L fermentor, 28 °C, pH = 7.4, 1.3 vvm, 650 rpm,192 h | 1.37 | 0.007 | Song et al. 2018 |
| S. roseosporus NBRC 12910 | Daptomycin | Cell immobilization on ultra-porous refractory brick flakes or silk sachets, airlift bioreactor | 10.0 g Glc, 30.0 g Dext, 20.0 g SoyF, 0.6 g Fe(NH4)2SO4, 0.2 g KH2PO4 | 2.0-L fermentor, 30 °C, pH = 7.0, 200 rpm, 132 h each cycle | 4.89 on refractory bricks and 3.62 on silk sachets | 0.005 (considering 8 cycles on refractory bricks and 6 cycles on silk sachets) | Chakravarty and Kundu 2016 |
| S. coelicolor M145 | Actinorhodin | Cell encapsulation in calcium alginate beads | 20.0 g Glc, 0.2 g CSA, 10.0 g YE, 42.0 g MOPS, 0.5 g K2SO4 , 20.2 g MgCl2 | Shake flask, 30 °C, pH = 6.8, 200 rpm, 192 h | 3.17 | 0.016 | López-García et al. 2014 |
| S. coelicolor M145 | Actinorhodin and undecylprodigiosin | Cell immobilization on PLA or PLA-plasma membranes | 20.0 g Glc, 200.0 g sucrose, 0.2 g CSA, 10.0 g YE, 42.0 g MOPS, 0.5 g K2SO4, 20.2 g MgCl2 | Shake flask, 30 °C, pH = 6.8, 200 rpm, 168 h | 0.28 and 0.015 | 0.016 and 8.92*10-5 | Scaffaro et al. 2017 |
| Streptomyces strain | Secondary metabolite | Mutagenesis and genome approaches | Fermentation medium (*1.0 L) | Growth conditions | Production (g·L-1) | Productivity (g·L-1· h-1) | Reference |
| S. hygroscopicus subs. ascomyceticus SA68 | Ascomycin | Femtolaser mutation and shikimic acid addition | 24.0 g Slb St, 40.0 g Dext, 5.0 g Pep, 7.0 g YE, 2.0 g CSL, 11.0 mL SoybO, 1.5 g Sh A, 0.5 g K2HPO4·3H2O, 1.5 g (NH4)2SO4, 1.0 g MgSO4·7H2O, 1.0 g CaCO3 | Shake flask, 28 °C, pH = 6.7, 200 rpm, 144 h | 0.45 | 0.003 | Qi et al. 2014a |
| S. hygroscopicus subs. ascomyceticus FS35 | Ascomycin | Addition of resin, of n-hexadecane, valine, lysine | 24.0 g Slb St, 40.0 g Dext, 5.0 g Pep, 7.0 g YE, 2.0 g CSL, 11.0 mL Soyb O, 1.5 g Sh A, 0.5 g K2HPO4·3H2O, 1.5 g (NH4)2SO4, 1.0 g MgSO4·7H2O, 1.0 g CaCO3 | Shake flask, 28 °C, pH = 6.7, 200 rpm, 144 h | 0.46 | 0.003 | Qi et al. 2014b |
| S. tsukubaensis TJ-01 | FK506 | UV and NTG mutagenesis, with selection for disodium malonate and disodium methylmalonate resistance. Genome shuffling and FK506 resistance. Dynamic fed-batch with disodium malonate and disodium methylmalonate addition. | 60.0 g St, 2.0 g YE, 2.5 Pep, 5.0 g Soyb M, 0.5 g K2HPO4, 0.5 g MgSO4, 0.5 g CaCO3 | 7.5-L fermentor, 28 °C, pH = 6.8, 200–1000 rpm, 1.0 vvm, 144 h | 0.51 | 0.003 | Du et al. 2014 |
| S. chattanoogensis L10 | Natamycin | WhiGch gene overexpression | 0.4 g Glc, 0.03 g YE, 0.03 g ME, 0.5 g TR | Shake flask, 30 °C, pH = 7.2, 250 rpm, 120 h | wt = 1.5, LG02 mut = 2.5 | wt = 0.012, LG02 mut = 0.021 | Liu et al. 2015 |
| S. avermitilis ATCC31267 | Avermectin B1a | Enhancement of aveR and malE genes expression by treating the strain with nanosecond pulsed electric field | 70.0 g Slb St, 16.0 g YE, 0.5 g K2HPO4·3H2O, 0.5 g MgSO4·7H2O, 4.0 g KCl, 10.0 mg CoCl2·6H2O, 2.0 g CaCO3 | Shake flask, 28 °C, pH = 7.0, 220 rpm, 120 h | 0.015 | 0.0001 | Guo et al. 2016 |
| S. avermitilis DQ03 | Ivermectin B1a | Construction of a biosynthetic gene cluster | 140.0 g CS, 0.1 g α-amylase, 28.0 g SoyF, 10.0 g YE, 0.022 g Na2MoO4·2H2O, 0.0023 g MnSO4·H2O, 0.25 g (NH4)2SO4, 0.02 g CoCl2, 0.8 g CaCO3 | Shake flask, 28 °C, pH = 7.5, 220 rpm, 240 h | 1.25 | 0.005 | Deng et al. 2019 |
CSA casamino acids, CS corn starch, CSL corn step liquor, Dext dextrin, DO dissolved oxygen, Glc glucose, ME malt extract, MOPS 3-morpholinopropane-1-sulfonic acid, NTG nitrosoguanidine, Slb St soluble starch, St starch, Pep peptone, PLA polylactic acid, Sh A shikimic acid, SoyF soybean flour, Soyb M soybean meal, Soyb O soybean oil, TR tryptone, WHd + RT wide-blade hydrofoil impeller and rushton turbine; YE yeast extract