New Insights on Steroid Biotechnology

被引:138
作者
Fernandez-Cabezon, Lorena [1 ,2 ]
Galan, Beatriz [1 ]
Garcia, Jose L. [1 ]
机构
[1] CSIC, Ctr Invest Biol, Dept Environm Biol, Madrid, Spain
[2] Tech Univ Denmark, Novo Nordisk Fdn Ctr Biosustainabil, Lyngby, Denmark
关键词
steroid; pharmaceuticals; actinobacteria; microbial cell factory; metabolic engineering; systems biology; RHODOCOCCUS-ERYTHROPOLIS SQ1; GENE-ENCODING 3-KETOSTEROID-DELTA(1)-DEHYDROGENASE; 3-KETOSTEROID; 9-ALPHA-HYDROXYLASE; MYCOBACTERIUM-SMEGMATIS; FUNCTIONAL-CHARACTERIZATION; TERMINAL OXYGENASE; MICROBIAL TRANSFORMATION; ARTHROBACTER-SIMPLEX; RHODOCHROUS DSM43269; TARGETED DISRUPTION;
D O I
10.3389/fmicb.2018.00958
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Nowadays steroid manufacturing occupies a prominent place in the pharmaceutical industry with an annual global market over $10 billion. The synthesis of steroidal active pharmaceutical ingredients (APIs) such as sex hormones (estrogens, androgens, and progestogens) and corticosteroids is currently performed by a combination of microbiological and chemical processes. Several mycobacterial strains capable of naturally metabolizing sterols (e.g., cholesterol, phytosterols) are used as biocatalysts to transform phytosterols into steroidal intermediates (synthons), which are subsequently used as key precursors to produce steroidal APIs in chemical processes. These synthons can also be modified by other microbial strains capable of introducing regio- and/or stereospecific modifications (functionalization) into steroidal molecules. Most of the industrial microbial strains currently available have been improved through traditional technologies based on physicochemical mutagenesis and selection processes. Surprisingly, Synthetic Biology and Systems Biology approaches have hardly been applied for this purpose. This review attempts to highlight the most relevant research on Steroid Biotechnology carried out in last decades, focusing specially on those works based on recombinant DNA technologies, as well as outlining trends and future perspectives. In addition, the need to construct new microbial cell factories (MCF) to design more robust and bio-sustainable bioprocesses with the ultimate aim of producing steroids a la carte is discussed.
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页数:15
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