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

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]