Table 1.

List of domains and associated reactions as implemented in BiGMeC

Abbrv.	Name	Note	Reaction
A	Adenylation	Activates and attaches AA to PCP	ATP + AA + PCP$\to$AA-PCP + AMP + Pii
ACP	Acyl carrier protein	Facilitates transport in PKSs
AT	Acyltransferase	Loads extender unit onto ACP	Acyl-CoA + ACP $\to$ Acyl-ACP + CoA
C	Condensation	Elongates the peptide by condensation	AA-PCP + Xn $\to$ Xn+1 + H2O + ACP
CAL	Coenzyme A ligase	Catalyzes the incorporation of different starter units, e.g. fatty acids, AHBA, and shikimic acid [32, 56, 57]	Y + PCP $\to$ Y-PCP + H2O
cMT	Carbon methyltransferase	Methylates peptide/polyketide	SAM + Xn $\to$ Xn + SAH
Cy	Heterocylization	Elongates the peptide by condensation and cyclization	AA-PCP + Xn $\to$ Xn+1 + H2O + ACP
DH	Dehydratase	Forms double bound by removal of H2O	Xn $\to$ Xn + H2O
E	Epimerase	Stereochemical inversion	Xn $\to$ Xn
ECH	Enoyl-CoA hydratase/isomerase	Not able to discriminate, so BiGMeC assumes isomerase	Xn $\to$ Xn
ER	Enoyl reductase	Reduces double bound formed by the DH domain to a methylene group	NADPH + H+ + Xn $\to$ Xn + NADP+
FkbH	FkbH-like domain	Domain in an alternative loading module. Dephosphorylates 1,3-bpg [58]	1,3-bpg + ACP $\to$ D-lactate-ACP + 2 Pi
GNAT	GCN5-related N-acetyl transferase	Alt. load module that decarboxylates malonyl-CoA and adds acetyl group to ACP [59]	Malonyl-CoA + ACP $\to$ Acetyl-ACP + CoA + CO2
KR	Keto reductase	Reduces carbonyl group to hydroxyl group	NADPH + H+ + Xn $\to$ Xn + NADP+
KS	Keto synthase	Appends extender unit to polyketide	Acyl-ACP + Xn $\to$ Xn+1 + CO2 + ACP
nMT	Nitrogen methyltransferase	Methylates peptide/polyketide	SAM + Xn $\to$ Xn + SAH
oMT	Oxygen methyltransferase	Methylates peptide/polyketide	SAM + Xn $\to$ Xn + SAH
PCP	Peptidyl carrier domain	Facilitates transport in NRPSs
TD	Thioester reductase	Releases product from ACP/PCP	NADPH + H+ + Xn $\to$ detached product + NADP+
TE	Thioesterase	Releases product from ACP/PCP	H2O + Xn $\to$ detached product

The peptide or polyketide backbone is referred to as X_n, and in reactions that extend the backbone we refer to the elongated backbone as X_n+1

AA, generic amino acid; 1,3-bpg, 1,3 biphosphoglycerate; CoA, Coenzyme A; P_ii, diphosphate; SAH, S-Adenosyl-L-homocysteine; SAM, S-Adenosyl methionine; Y, generic starter unit