Hybrid PKS-NRPS synthetase; part of the gene cluster that mediates the biosynthesis of the mycotoxins cytochalasins E and K (PubMed:21983160). The hybrid PKS-NRPS synthetase ccsA and the enoyl reductase ccsC are responsible for fusion of phenylalanine with an octaketide backbone and subsequent release of the stable tetramic acid precursor (PubMed:21983160, PubMed:27551732). The polyketide synthase module (PKS) of the PKS-NRPS ccsA is responsible for the synthesis of the octaketide backbone (PubMed:21983160). The downstream nonribosomal peptide synthetase (NRPS) amidates the carboxyl end of the octaketide with a phenylalanine (PubMed:21983160). A reductase-like domain (R) at the C-terminus catalyzes the reductive release of the polyketide-amino acid intermediate (PubMed:21983160). Because ccsA lacks a designated enoylreductase (ER) domain, the required activity is provided the enoyl reductase ccsC (PubMed:21983160, PubMed:27551732). Upon formation of the 11-membered carbocycle-fused perhydroisoindolone intermediate, a number of oxidative steps are required to afford the final cytochalasin E and K, including two hydroxylations at C17 and C18, one alcohol oxidation at C17, one epoxidation at C6 and C7 and two Baeyer-Villiger oxidations (PubMed:21983160). The oxidative modification at C17, C18 and the C6-C7 epoxidation are likely to be catalyzed by the two cytochrome P450 oxygenases ccsD and ccsG (PubMed:21983160). CcsD may be responsible for the epoxidation of the C6-C7 double bond (PubMed:21983160). CcsG may be responsible for the successive oxidative modifications at C17 and C18 (PubMed:21983160). The double Baeyer-Villiger oxidations of ketocytochalasin to precytochalasin and cytochalasin Z(16) are among the final steps leading to cytochalasin E and K and are catalyzed by ccsB (PubMed:21983160, PubMed:24838010). The first oxygen insertion step follows that of the classic BVMO mechanism, generating the ester precytochalasin (PubMed:24838010). Release of precytochalasin into an aqueous environment can generate the shunt product iso-precytochalasin through spontaneous isomerization (PubMed:24838010). Alternatively, precytochalasin can undergo further oxidation by ccsB to yield the in-line carbonate-containing cytochalasin Z(16) (PubMed:24838010). Cytochalasin Z(16) is a precursor to cytochalasin E and cytochalasin K, whereas iso-precytochalasin is a precursor to cytochalasin Z(17) and rosellichalasin (PubMed:21983160, PubMed:24838010). The hydrolyase ccsE may catalyze hydrolysis of epoxide bond in cytochalasin E to afford cytochalasin K (PubMed:21983160). The function of ccsF has not been assigned but it may play a role in post-PKS-NRPS biosynthetic step, resistance or transport of cytochalasins and related PKS-NRPS products (PubMed:21983160). Mycotoxin biosynthesis. NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, epimerase (E) domains (responsible for l- to d- amino acid conversion) are present within the NRP synthetase (By similarity). CcsA contains also a polyketide synthase module (PKS) consisting of several catalytic domains including a ketoacyl synthase domain (KS), an acyl transferase domain (AT), a dehydratase domain (DH), a methyltransferase domain (MT), and a ketoreductase domain (KR). Instead of a thioesterase domain (TE), CcsA finishes with a reductase-like domain (R) for peptide release. CcsA has the following architecture: KS-AT-DH-KR-PCP-C-A-T-R (PubMed:21983160). Loss of cytochalasin E and cytochalasin K production. In the C-terminal section; belongs to the NRP synthetase family.