Table 2.
Process variables for microbial androstenedione (AD) and androstadienedione (ADD) production, from the most relevant scientific articles and patents found in a systematic search.
| Microorganism 1 | Substrate | Genetic Modifications | Reactional Conditions | Results | Differential | Ref. |
|---|---|---|---|---|---|---|
| Scientific Articles | ||||||
| Mycolicibacteriumneoaurum TCCC 11978 (MNR M3) | Sterol mixture, weight percentage: 51.7% β-sitosterol, 27.2%; stigmasterol, 17.1% campesterol, and 4.0% brassicasterol—Soybean oil | Cofactor engineering: modification of enzymes related to NADH * and NAD+ * metabolism | pH: 7.2; 30 °C; 140 rpm; 144 h | conversion ratio 94% | nicotinic acid in the phytosterols fermentation system to increase intracellular NAD+/NADH | [28] |
| Mycolicibacterium neoaurum TCCC 11979 | Phytosterol (98.4% purity) | - | 29 °C; 140 rpm; 120 h | molar yield of AD 55.8% | Oxygen vectors (n-hexadecane, perfluorohexane, soybean oil, PDMS, and PMPS *) | [59] |
| Mycolicibacteriumneoaurum TCCC 11978 (MNR M3) | Sterol mixture, weight percentage: 51.7% β-sitosterol, 27.2% stigmasterol, 17.1% campesterol, and 4.0% brassicasterol | Overexpression of cytochrome p450 125 (cyp125-3) | pH: 7.2; 30 °C; 140 rpm; 120 h | Conversion: 96%; 1.98 g·L−1 in 96 h | phytosterols (3 g·L−1) and HP-β-CD ** (25 mM) | [81] |
| Mycolicibacteriumneoaurum TCC 11028 (MNR M3) | Phytosterol (98.4% purity/3 g·L−1) | Overexpression of nicotinic acid phosphoribosyltransferase (NAPRTase) | pH 7.2; 29 °C; 200 rpm; 96 h | molar yield of AD (D) (94.9%) | HP-CD ** (0 or 25 mM) | [90] |
| Mycolicibacterium neoaurum NwIB-R10hsd4A | Phytosterol | - | T1 30 °C; T2 37 °C | 24.7 g·L−1 | two-step bioprocess, cell culture at 30 °C and bioconversion with resting cells at 37 °C | [104] |
| Mycolicibacterium sp. VKM Ac-1817D | Phytosterol | - | 30 °C; 200 rpm | 11 mmol/L; 0.3 mmol/h/g dry cell | MCD **** | [39] |
| Mycolicibacterium sp. | 4.5% β-sitosterol; 26.4% campesterol; 17.7% stigmasterol; 3.6% brassicasterol | Deletion kshA1 and kstD1 ***** | pH = 8; T = 37 °C; 200 rpm; 72 h | AD, 3.1 g·L−1 | HP-β-CD ***; increase in culture temperature to 37 °C to reduce nucleus degradation | [64] |
| Mycolicibacterium neoaurum NwIB-01 | Soybean phytosterols | Inactivation and augmentation of the primary 3-Ketosteroid-δ1-Dehydrogenase | 30 °C; 300 rpm; airflow 0.5 vvm; 96 h | ADD, 4.23 g·L−1; AD, 1.76 g·L−1; (57.8% mole conversion) | - | [62] |
| Mycolicibacterium sp. MB 3683 | Phytosterol | - | 30 °C; 200 rpm; 30 h | 1.3–1.4 g·L−1 | Cholinium; amino acids Ionic liquids; Best: 1% (v/v) [Ch][Asp] | [38] |
| Mycolicibacterium neoaurum TCCC 11978 C2 | 51.7% sitosterol; 27.2% stigmasterol; 17.1% campesterol; 4.0% brassicasterol | - | 30 °C; 140 rpm; 120 h | 84.8% mole conversion | HP-β-CD *** | [102] |
| Mycolicibacterium neoaurum, Pimelobacter simplex, and Rhodococcus erythropolis | soybean sterols (20–30 g/L) | - | 30 °C; 220 rpm; phytosterol load of 30 g/L over 144 h | AD: 14.5–15.2 g·L−1 | Mixture of soy steroids (20–30 g/L) in the form of small crystals in suspension (particle size 5–15 μm) | [33] |
| Mycolicibacterium sp. DSM-2967 | phytosterol-containing vegetable oils | - | pH 7.8; at room temp.; 200 rpm | Best: with canola oil; yield: 7.92 mg/100 mL | Phytosterol-containing vegetable oils directly converted to AD | [105] |
| Mycolicibacterium sp. MB 3683 | Phytosterols | - | Ionic liquid addition at 84 h, 20:1 (v/v, aqueous/IL), | AD production reached 2.23 g·L−1 after 5 days | Ionic liquid to increase low substrate solubility | [114] |
| Alkalibacterium olivoapovliticus | olive oil | - | 72 h; 30 °C | Conversion: 90% | Concrete was used as a tool to immobilize the microorganism | [109] |
| Moraxella ovis | Rice bran oil (RBO) | - | 36 h, pH 7; 30 °C | 0.22 mg AD/40 mg RBO | The unsaponifiable matter of rice bran oil was used as a raw material | [71] |
| Mycolicibacterium sp. B-3805S/Mycolicibacterium sp. NRRL B-3683 | Phytosterol | nitrosoguanidine (NTG) mutagenesis | 5-L surface-aeration microprocessor-controlled fermentor; 30 °C | Conversion: 70.6% | - | [4] |
| Patents | ||||||
| Mycolicibacterium phlei NRRL B-8154 | Sitosterol, cholesterol, stigmasterol and campesterol | Nitrosoguanidine mutagenesis | 30 °C; 14 days | - | - | [120] |
| Mycolicibacterium fortuitum EUG-119 (KCCM-10259) | Cyclodextrin-sterol complex | - | 30 °C; 5 days; 200 rpm | - | - | [121] |
| Mycolicibacterium sp. NRRL B-3805 | Alpha-sitosterol (AS) | - | 30 °C; 4 days; 220 rpm | 160 mg AD/1000 mg AS | - | [122] |
1 The microbial species names used are the ones re-classified by Gupta et al. [120] but that are mentioned in the cited manuscripts as the original names: Mycolicibacterium sp. (mentioned as Mycobacterium sp.); Mycolicibacterium neoaurum (mentioned as Mycobacterium neoaurum); Mycolicibacterium fortuitum (mentioned as Mycobacterium fortuitum); Mycolicibacterium phlei (mentioned as Mycobacterium phlei). * NADH and NAD+: Nicotinamide adenine dinucleotide (reduced and oxidized, respectively). ** PDMS polydimethylsiloxane and PMPS polymethylphenylsiloxane. *** HP-β-CD hydroxypropyl-β-cyclodextrin. **** MCD methylated β-cyclodextrin. ***** kshA1 and kstD1: Genes involved in the expression of the enzymes 3-ketosteroid-9α-hydroxylase (Ksh) and 3-ketosteroid-1-dehydrogenase (KstD), respectively.