eISSN 1738-8872
pISSN 1017-7825
pISSN 1017-7825
Table. 4.
Table. 4.
Representative examples of
| Heterologous host | Engineering | Target genes or regions | Deletion method | Expressed BGC | BGC vector | Effect | Limitation | Ref |
|---|---|---|---|---|---|---|---|---|
| BGC deletion and Pleiotropic gene engineering | Deletion of four BGCs (ACT, RED, CPK, and CDA) Point mutations of rpoB and rpsL. | Homologous recombination by double crossover of the plasmid | Shlorampheniocol and congocidine | Cosmid | Improved production, clean profile of background metabolites | Low fitness | [104] | |
| BGC deletion | Deletion of three BGCs (candicidin, type III PKS, and type I PKS) | Homologous recombination by double crossover of the plasmid | None | None | Improved fitness, sporulation, and clean profile of background metabolites | Heterologous expression was not tested | [124] | |
| BGC deletion | Deletion of three BGCs (ACT, RED, and CDA) One copy integration of AfsRS by attB integrase | Homologous recombination by double crossover of the plasmid | Streptothiricins, borrelidin, and linear lipopeptides | BAC | High-throughput functional genome mining of |
Low fitness, laborious screening of BAC libraries | [123] | |
| BGC deletion | Deletion of three BGCs (ACT, RED, and CDA) Additional copies integration of AfsRS by attB integrase | Homologous recombination by double crossover of the plasmid | Hybrubins | BAC | High-throughput functional genome mining of |
Low fitness | [140] | |
| BGC deletion | Deletion of fifteen BGCs (Frontalamide, Paulomycin, Geosmin, Lantibiotic, carotenoid, flaviolin, candicidin, antimycin, 2 PKSNRPS, and 4 NRPS) | Homologous recombination by double crossover of the plasmid using λ-red system | Tunicamycin B2, moenomycin M, griseorhodin A, pyridinopyrone A, bhimamycin A, didesmethylmensacarcin, didemethoxyaranciamycino ne, aloesaponarin II, and cinnamycin, fralnimycin | Fosmid and BAC | Improved production, clean profile of background metabolites | Moenomycin M productivity was reduced. | [122] | |
| Nonessential region deletion and BGC deletion | Deletion of 1.48 Mb left arm determined by comparative genomics | Homologous recombination by double crossover of the plasmid using λ-red system Cre/loxP system | Streptomycin, cephamycin C, and pladienolide | Cosmidand BAC | Improved production by additional introduction of regulatory gene and optimization of codon usage | Low conjugation efficiency | [103] | |
| Nonessential region deletion | Deletion of 1.48 Mb left arm and some regions determined by comparative genomics | Homologous recombination by double crossover of the plasmid using λ-red system Cre/loxP system | Streptomycin, ribostamycin, kasugamycin, pholipomycin, oxytetracycline, resistomycin, pladienolide B, erythromycin A, bafilimycin B1, nemadectin α, aureothin, leptomycin, cephamycin C, holomycin, lactacystin, clavulanic acid, rebeccamycin, novobiocin, chloramphenicol, 2-methylisoborneol, pentalenolactone, amorpha-1,4-diene, taxa-4,11-diene, levopimaradiene, and abietatriene | Cosmid and BAC | Improved production, fitness, clean profile of background metabolites. Broad precursor capacity (sugar, polyketide, peptide, shikimate, and MVA or MEP) | Ribostamycin, oxytetracycline productivity were reduced | [125] | |
| Nonessential region deletion | Deletion of 1.3 Mb and 0.7 Mb nonessential arms determined by comparative genomics and prediction tools | Cre/loxP recombination | ACT | pMM1 | Improved production, fitness, ATP, NADPH, transformation efficiency, and genetic stability. Dispersed morphology. | 1.3 Mb deleted strain was detrimental due to deletion of some unknown genes | [121] | |
| Pleiotropic gene engineering and BGC deletion | Deletion of |
Homologous recombination by double crossover of the plasmid using λ-red system | ACT | Fosmid | Improved production, fitness, and NADPH. | Undesirable effects might be incurred due to the global change of transcriptome | [128] |
J. Microbiol. Biotechnol. 2019;29:667~686 https://doi.org/10.4014/jmb.1904.04015
© J. Microbiol. Biotechnol.