## 4 Renewable Carbon Sources for the Biosynthesis of 3-HP
### Microbial Production of 3-HP from Acetic Acid, Ethanol, and Fatty Acids  
Fatty acids, acetic acid, and ethanol are converted to acetyl-CoA, which is further metabolized for cell growth and product synthesis. Acetyl-CoA is an important precursor for the synthesis of 3-HP, and all three substances are high-quality carbon sources for the production of 3-HP via the malonyl-CoA pathway. At present, several methods have been developed to convert lignocellulosic biomass and C1 gas into acetate [94]. Recently, acetate has been considered as a potential fermentation substrate, and many studies have attempted to convert acetate into biofuels. However, acetate is less efficiently assimilated by microorganisms than glucose. In a study by [PERSON] et al. [77], acetate consumption was increased by upregulating genes related to acetate assimilation and activating the glyoxalate cycle, and metabolic spillover was prevented by inhibiting the expression of genes related to fatty acid synthesis. Finally, the engineered _E. coli_ introducing the malonyl-CoA pathway produced 3 g/L of 3-HP in shake flasks. Similarly, [PERSON] et al. [34] synthesized 15.8 g/L of 3-HP with the yield of 0.71 g/g from acetate, using engineered _E. coli_ via the malonyl-CoA pathway. Subsequently, the titer of 3-HP reached 11.2 g/L with the yield of 0.55 g/g when syngas-derived acetic acid was used as a substrate instead of pure acetic acid. Due to the inefficient growth of microorganisms on acetate, a two-stage strategy was developed for the synthesis of 3-HP in engineered _E. coli_ that used glucose for cell growth and acetate for 3-HP formation. Finally, the strain produced 7.3 g/L of 3-HP in the two-stage bioreactor [95]. Notably, it is important to balance the TCA cycle and the pathway for 3-HP production, since the whole process from acetate to 3-HP requires the provision of additional reducing power and energy. [PERSON] et al. [47] achieved a balance between the TCA cycle and 3-HP synthesis by regulating the expression of citrate synthase, and the engineered _C. glutamicum_ produced the highest titer of 3-HP from acetate reported to date, reaching 17.1 g/L. Ethanol can be efficiently synthesized from starch, sugar, lignocellulosic biomass, and C1 gas. Compared to acetate, there are several advantages to utilizing ethanol as a substrate. Instead of consuming one mole of ATP, two moles of NADH are produced when ethanol is assimilated to acetyl-CoA. In addition, the pH of the fermentation broth does not change when ethanol is consumed as a substrate. Recently, it has been demonstrated that _E. coli_ has the potential to utilize ethanol to produce 3-HP. [PERSON] et al. [35] increased the titer of 3-HP by optimizing the expression levels of genes in the ethanol utilization pathway and the malonyl-CoA pathway, and explored the effect of deleting or modifying key genes associated with the oxidative branch of the TCA cycle and the gluconeogenesis pathway on 3-HP production. The engineered _E. coli_ reached a titer and yield of 13.17 g/L and 0.57 g/g in the whole-cell catalytic system. The low titers of 3-HP from ethanol or acetate as substrates are probably attributed to the fact that these substrates tend to be accumulated as electron acceptors during microbial fermentation, rather than assimilated by microorganisms. Fatty acids (FAs) are a cheap by-product of the palm oil industry that can effectively provide acetyl-CoA for 3-HP production. Reducing equivalents and ATP are produced during the assimilation of FAs via the \(\beta\)-oxidation pathway. It is worth noting that the theoretical yield of 3-HP from glucose or glycerol was 1 g/g, while from 16-carbon FAs it was 2.49 g/g, which was much higher than from other substrates. To date, the highest 3-HP titer achieved in the malonyl-CoA pathway is 52 g/L, which was produced by an engineered _E. coli_ that can efficiently utilize FAs [36].