**4. Phenolic**

*Saccharomyces*

**3. Alkaloids**

*in secondary metabolite formation.*

**Figure 1.**

hypertensive) [15].

The methods and technology used to improve pharmaceutical production of secondary metabolites in the *S. cerevisiae* have advanced rapidly in recent years. We discuss below the progress in developing biosynthetic pathways of *Saccharomyces cerevisiae*' secondary metabolites with anticancer potential: alkaloids,

*A short description of the formation pathways of secondary metabolites [11, 12]. Four sub-groups of microorganism and plant-generative metabolites involve terpenoids, polyketides, non-ribosomal peptides and alkaloids. Biosynthetic genes (BGC's) are structurally classified into the genes that encrypt major biosynthetic enzymes, supplementary enzymes, precursors in the process of biosynthesizing, resistance factors or transporters* 

phenolic, terpenoids, polyketides, non-ribosomal peptides, and vitamin C.

Several studies have used *S. cerevisiae* in recent years as a host to engineer the biosynthetic process of alkaloids. Alkaloids are complex nitrogen molecules that are extremely bioactive. There are reportedly approximately 50 alkaloid medications, including vincristine (cancer drug), codeine (analgesic drug) and noscapine (antitussive drug). They are unique for the cell cycle and the process, because they block metaphase (M phase) in mitosis. They block tubulin's ability to form microtubules via polymerization. Dysfunctional spindle structures, avoid chromosome separation and cell proliferation. Strictosidine, which had been synthesized by novo, was the earliest study of alkaloid plant origin in *Saccharomyces cerevisiae* strains [14]. Strictosidine is a significant intermediate product in the terpenoids Indole alkaloids (TIAs) biosynthesis that include vincristine (antitumor) and ajmalicine (anti-

The metabolic course of *Saccharomyces cerevisiae* for protoberberine alkaloid (S) canadine from racnorlaudanosolin has been optimized by Galanie et al. [16]. The secondary metabolite of Berberine has numerous pharmacological effects, such as antidiabetics, antibacterial, anti-ulcerones and anti-inflammatory effects. In vivo and vitro experiments with berberine, the results of arresting cell cycle during G1 or G2/M and apoptosis of tumor cell were shown to be anti-cancer activity. Berberine also was found to induce autophagy and stress in the endoplasmic reticulum, resulting in the invasion and inhibition of the tumor cells. Berberine has been proven to lower angiogenesis by decreasing expression of VEGF in addition to its apoptotic effects. The cancer cell migration was also decreased. In the respective

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Phenolic are a large category of secondary plant metabolites that have at least one hydroxylated ring. Flavonoids and stilbenes are two groups of metabolites highly appreciated as a nutrient and therapeutic agent among the phenolic developed by phenylpropanoid pathways in the plant [18]. As a host cell, *Saccharomyces cerevisiae* is well equipped to promote phenolic compound biosynthesis. The following phases include cancer development: initiation, development, proliferation, invasion and metastasis. Initiation links by free radicals, inflammatory mediators, radiation, smoke of cigarette that damage the DNA-product, which can cause genetic mutation and replication of cells which are mutated results to cause carcinogenesis [19].

It has been noted that phenolic compounds i.e. ellagic acid and delphinidin show significant protective effects for example, apoptotic activity in colon cancer cells. In prostate, liver and leukemia cancer cells, delphinidin also showed significant activity. Cell apoptosis can also be caused by phenolic compounds. The mechanisms of invasion and migration of human cancer are also updated (**Figure 2**) [20].

**Figure 2.** *Potential of secondary metabolite protective mechanisms for cancer management [17].*
