Table 1.
Microbial production of steroidal intermediates from natural sterols by recombinant DNA technology approaches.
| Parental Strain | Main product | Genetic manipulations |
|---|---|---|
| M. neoaurum NwlB-01 | ADD | Overexpression of an endogenous kstD gene or a heterologous kstD gene derived from the bacterium Arthrobacter simplex (Wei et al., 2010b, 2014) |
| R. equi USA-18 | ADD | Deletion of the kshB1 gene (Yeh et al., 2014) |
| M. neoaurum ATCC 25795 | AD/ADD | Deletion of the kshA1 and kshA2 genes (strain named NwIB-XII) (Xu et al., 2016) |
| M. smegmatis mc2155 | (1) AD (2) ADD |
(1) Deletion of the kshB1 and kstD1 genes (strain named MS6039-5941); (2) Deletion of the kshB1 gene (strain named MS6039) (Galán et al., 2017b) |
| M. neoaurum ATCC 25795 | 9OH-AD | Multiple deletion of several kstD genes and overexpression of an endogenous kshA gene (Yao et al., 2014) |
| Mycobacterium sp. NRRL B-3805 | 9OH-AD | Overexpression of the kshA and kshB genes of M. smegmatis mc2155 and G. neofelifaecis NRRL B-59395, respectively (Yuan et al., 2015) |
| R. rhodochrous DSM43269 | 1,4-HBC | Multiple deletion of all the kshA genes (ΔksA12345) (Petrusma et al., 2011; Wilbrink et al., 2011) |
| M. neoaurum ATCC 25795 | (1) 4-HBC (2) 1,4-HBC (3) 9OH-4-HBC |
(1) Deletion of multiple kshA and kstD genes (ΔkstD123, ΔkshA12) and hsd4A gene; (2) Deletion of multiple kshA genes (ΔkshA12) and the hsd4A gene; (3) Deletion of multiple kstD genes (ΔkstD123) and the hsd4A gene (Xu et al., 2016) |
| M. smegmatis MS6039-5941 (Galán et al., 2017b) | TS | Overexpression of two genes encoding 17b-HSDs from Comamonas testosteroni and Choliobolus lunatus (Fernández-Cabezón et al., 2017a) |
Several examples of actinobacterial strains designed by Metabolic Engineering approaches for this purpose are shown. Main end products obtained at the bioconversions and no other by-products are indicated. ADD, 1,4-androstadiene-3,17-dione; AD, 4-androstene-3,17-dione; 9OH-AD, 9α-hydroxy-4-androstene-3,17-dione; TS, 17β-hydroxy-4-androstene-3,17-dione; testosterone; 1,4-HBC, 22-hydroxy-23,24-bisnorchol-1,4-diene-3-one; 4-HBC, 22-hydroxy-23,24-bisnorchol-4-ene-3-one; 9OH-4-HBC, 9,22-dihydroxy-23,24-bisnorchol-4-ene-3-one.