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Table 1 Metabolic engineering approaches used for enhancing the production of diverse macrolides

From: Engineering actinomycetes for biosynthesis of macrolactone polyketides

Compound Strain Approach References
Native host
 Epothilone Sorangium cellulosum Expression of propionyl-CoA synthetase, which converts propionate into propionyl-CoA, the precursor of methylmalonyl-CoA [148]
 Nargenicin A1 Nocardia sp. CS682 Over-expression of ACCase complex for enhancement of production [82]
 Natamycin S. chattanoogensis L10 Overexpression of the endogenous PPTase SchPPT for enhancement of production [149]
 Tylosin S. fradiae Different approaches for enhancement of production titer: SARP regulators tylS and tylR are overexpressed Inactivation of a transcriptional repressor (tylQ) Diruption of tylP encoding a γ-butyrolactone receptor [150,151,152]
 Spiramycin S. ambofaciens Overexpression of pathway-specific regulator srm22 or srm40 increased spiramycin production [153]
 Milbemycin S. bingchenggensis Enhancement by overexpression of pathway-specific regulator milR [154]
 Pikromycin S. venezuelae Enhancement of production by overexpressing genes of branched chain amino acids catabolism [83]
 Stambomycins S. ambofaciens Overexpression of pathway-specific regulator samR0484 triggers production of cryptic BGC [155]
Heterologous hosts
 FK 506 S. clavuligerus CKD1119 Expression of mutB from S. erythraea [156]
 Methoxymalonate-platenolide analog S. fradiae Introducing the biosynthetic pathway for methoxycarbonyl-ACP [112]
 Midecamycin S. fradiae Enhancement of production by introducing the biosynthetic pathway for methoxylmalonyl-ACP from the FK520 producer S. hygroscopicus [112]
 Pikromycin S. venezuelae Enhancement of production by expression of two global regulators, metK1-sp and afsR-sp, from Streptomyces peucetius [157]
 Tylosin S. venezuelae Overexpression of pikD, a pathway-specific regulator from pikromycin biosynthetic pathway [158]