**2. Polyketide Synthases Type I**

The type I polyketide synthases (type I PKSs) involve huge multifunctional proteins that have many modules containing some domains, in which a particular enzymatic reaction occurs (Figure 2). Each module has the responsibility of performing one condensation cycle in a non-iterative way. Because this system works with some modules, it is also called modular PKS. The essential domains existing in each module are acyltransferase (AT), keto synthase (KS), and acyl carrier protein (ACP) which collaborate to produce β-keto ester intermediate. In addition, the other domains that may be present in the module are β-ketoreductase (KR), dehydratase (DH), and enoyl reductase (ER), which are responsible for keto group modification. In the process of producing polyketide, the expanding polyketide chain is transferred from one module to another module until the completed molecule is liberated from the last module by a special enzyme [2,26,31].

**Figure 2.** Structure of type I PKSs with three modules and 15 domains. ACP, acyl carrier protein; AT, acyltransferase; KS, ketosynthase; KR, ketoreductase; DH, dehydratase; ER, enoylreductase.

Furthermore, type I PKSs are generally responsible for producing macrocyclic polyketides (macrolides), although there was also a study reporting that type I PKSs are also involved in the biosynthesis of linear polyketide tautomycetin [32]. Macrolide belongs to a polyketide compound characterized by a macrocyclic lactone ring, which has various bioactivities such as antibacterial, antifungal, immunosuppressing, and anticancer. As an antibacterial agent, macrolide works by inhibiting protein synthesis by binding to the 50S ribosomal subunit and blocking the translocation steps of protein synthesis [8,27,33]. Some examples of macrolides produced by *Streptomyces* are rapamycin, FK506, spiramycin, avermectin, methymycin, narbomycin, and pikromycin, as shown in Figure 3 [34–37]. These compounds were produced by multifunctional polypeptides encoded by a biosynthetic gene cluster. The list of some polyketides produced by *Streptomyces* with their huge multifunctional proteins can be seen in Table 1.
