Fed-batch
Pecyna et al.(Pecyna and Bizukojc 2011) showed that the application of
glycerol feed, when lactose is the initial substrate, leads to the
appreciable lovastatin concentration in the broth (122.4 mg/L),
nevertheless the abundant (+)-geodin level is at the same time obtained
(255.5 mg/L). The cultures with glycerol as the initial substrate and
fed with lactose produce less lovastatin and (+)-geodin. The application
3of the various combined glycerol and/or lactose feeds allows for
improving lovastatin production up to 161.8 mg/L. Porcel et al.(Porcel,
López et al. 2008) showed that semi-continuous operation enhanced
productivity of lovastatin by 315% compared with a conventional batch
operation.
2.2 Statins produced in
SSF
Solid-state fermentation (SSF) has the advantages of simple operation,
low energy consumption, easy control of fermentation process, relatively
low requirement for sterility, and not easy to occur large area
pollution. The main media of solid-state fermentation (SSF) are
agricultural raw materials, including corn, rice, sorghum, barley and so
on. Biomass is a kind of renewable and clean energy. The rational,
efficient development and utilization of biomass is also a hot spot for
Solid-state fermentation (SSF) to produce statins. In fact, the carrier
used in the fermentation process and the surface wind speed can also
affect the fermentation of microorganisms to produce statins.
Solid-state fermentation for statins biosynthesis was summarized in
Table 3.
2.2.1 Medium
Different medium has great
influence on lovastatin production by microbial solid-state
fermentation. Valera et al.(Valera, Gomes et al. 2005) found that wheat
bran was to be the most suitable substrate to yield 16.65 mg/g
lovastatin in aerated stirred beds after 6 days of fermentation byA. flavipes BICC 5174. Atlı et al. (Atlı, Yamaç et al. 2015)
showed that a maximum lovastatin titer of 139.47 mg/g was achieved by
the fermentation of 5 g of barley,
1–2 mm particle diam, at 28 °C. Subhagar et al.(Subhagar, Aravindan et
al. 2009) showed barley, long grain rice and sago starch were the
suitable substrates producing. The maximum titer of lovastatin are
193.7 mg/g, 190.2 mg/g and
180.9 mg/g,respectively. Suraiya et
al.(Suraiya, Kim et al. 2018) showed that glucose had the greatest
influence on the production of lovastatin. Under the optimal
fermentation parameters, the average titer of lovastatin reached 13.98
mg/gds using M. purpureus KCCM 60168. Pansuriya et al.(Pansuriya
and Singhal 2010) also did this work. The titer of lovastatin was to
3.723 mg/g by A. terreus UV 1718 using solid-state fermentation
when optimizing the fermentation parameters.
Different medium also has great influence on compactin production by
microbial solid-state fermentation. Shaligram et al.(Shaligram, Singh et
al. 2008) showed that the optimal production of compactin was 0.771
mg/gds with the addition of various supplements (glycerin, etc.) byP. brevicompactum WA 2315. The titer of compactin was increased
to 0.815 mg/gds when the pH of the supplement solution was 7.5.
Shaligram et al.(Shaligram, Singh et al. 2008) optimized the synthesis
of compactin by P. brevicompactum WA 2315. The final titer of
compactin was increased from 0.45 mg/gds to 1.25 mg/gds by adding
glycerol during fermentation. Syed et al.(Syed, Rajendran et al. 2014)
showed that the combinations of the substrates with 1.5 g of green peas,
1.5 g of millet and 1.5 g of ragi gave maximum production of 389.34
mg/gds compactin by A. terreus MTCC 279.
Biomass is a kind of renewable and clean energy. The rational, efficient
development and utilization of agricultural waste as the substrate of
solid-state fermentation (SSF) to produce statins can not only save
production cost effectively, but also realize the effective utilization
of resources. Iewkittayakorn et al.(Iewkittayakorn, Kuechoo et al. 2020)
showed that the titer of lovastatin reached the highest at 0.99 mg/g
after 14 days of fermentation with soybean sludge as substrate by adding
addition palm oil. Javed et al.(Javed, Bukhari et al. 2016) studied the
production of compactin by solid-state fermentation of with bagasse as
substrate by A. terreus GCBL-03. Bagasse was pretreated by
potassium hydroxide readily become available to microorganism, leading
to 30.63±1.24 mg/100mL.
2.2.2 Other effects