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