Fig.1 Growth morphology of strain C23-3 before and after chemical regulation（cultured for 28 days） A：The left column shows the cultures in seawater potato liquid medium,and the right column is for brown rice medium;the photos from top to bottom are experimental groups added 3-amino-L-tyrosine,3-hydroxy-L-tyrosine,3-nitro-L-tyrosine,3,4-dihydroxyphenylpyruvate,farnesol,MSB and H2O2,respectively. B：The top is for the seawater potato liquid medium,and the bottom is for the brown rice medium;the 3 columns on the left are the experimental groups with FPP,and the last column on the right is the experimental group with L-selenomethionine. C：The top is for the seawater potato liquid medium,and the bottom is for the brown rice medium;the photos from left to right are the solvent control groups supplemented with sterile water,DMSO and 5% HCl and blank control groups. The labels below the picture are the concentrations of the inducers added. For each of the above groups,two repeats were set

Fig.2 TLC fingerprints of strain C23-3 fermentation products before and after chemical regulation（brown rice medium） A1-C1：UV images under 254 nm;A2-C2：fluorescence images under 365 nm;A3-C3：images of colorization by anisaldehyde-sulfuric acid reagent;A4-C4：images of 1,1-Diphenyl-2-picryl-hydrazyl（DPPH）free radical scavenging bioautography;A5-C5：images of colorization by potassium ferricyanide-ferric chloride reagent;A6-C6：images of acetylcholinesterase inhibitory bioautography. Abbreviations：Farnesyl pyrophosphate ammonium salt to FPP,menadione sodium bisulfite to MSB

Fig.3 Molecular network and its partial enlarged diagram of the metabolites of strain C23-3 under different cultural condi-tions based on MS2 relationships A1 and A2：Enlarged images of ion clusters of butyrolactone I congeners;B：enlarged images of ion clusters of territrem B congeners;C：enlarged images of ion clusters of lovastatin congeners. Compounds 1-4：butyrolactone I,territrem B,lovastatin,and lovastatin hydroxy acid. Compounds 5-13：Possible derivatives of known compounds,i.e.,[M（butyrolactoneⅠisomer）+H]+,[M（butyrolactoneⅠ-2H）+H]+,[M（butyrolactoneⅠisomer+O）+H]+,[M（butyrolactone I-H2O）+H]+,[M（territrem B-O）+H]+,[M（territrem B-CH2）+H]+,[M（lovastatin-H2O）+H]+,[M（lovastatin-O）+H]+,and[M（lovastatin+2H）+H]+,respectively. The nodes in the molecular network are marked in 15 colors, ,sequentially representing the 15 sample sources of compounds：induction groups with the addition of 3-amino-L-tyrosine（1 mmol/L）,3-hydroxy-L-tyrosine（10 mmol/L）,3-nitro-L-tyrosine（10 mmol/L）,3,4-dihydroxyphenylpyruvate（1 mmol/L）,farnesol（1 µmol/L）,FPP（5 μmol/L）,MSB（10 µmol/L）,H2O2（1 mmol /L）and selenomethionine（61 mmol/L）;blank groups cultured for 14 d and 28 d;reagent control groups supplemented separately with 5% HCl,DMSO,and sterile water（the sterile water group cultures for 14 d and 28 d,respectively）

Fig.4 Base peak chromatograms of the metabolites of strain C23-3 under different culture conditions A-C are the LC-MS base peak chromatograms of the induction groups added with analogs of small molecule precursor tyrosine/4-hydroxyphenylpyruvate（3-amino-L-tyrosine,3-hydroxy-L-tyrosine,3-nitro -L-tyrosine and 3,4-dihydroxyphenylpyruvate）,oxidative stress agents MSB and H2O2）,L-selenomethionine,and analogs of natural terpenoid side chain donor dimethylallyl diphosphate FPPand farnesol）,their corresponding blank groups and solvent control groups. Except for the specified “14 d” groups,which are for the 14 d culture extracts,the other groups were cultured for 28 d. The group name is marked in the upper left corner of each base peak chromatogram. The black frames label butyrolactone I,the blue ones label territrem B,the purple ones label lovastatin,and the green ones label lovastatin hydroxy acid;the arrows indicate variant metabolites

Fig. 5 MS2 spectra of compound 1 and its possible derivatives The labeling of Compounds 1 and 5-8 follows the same numbers as in Fig.3. The similarity values represent the cosine values of the similarity comparison between detected compounds in samples and the pure compounds recorded in GNPS database or the annotated known compound 1 or compound 5 by GNPS molecular networking（the red circles in Fig.5 mark the corresponding series of fragment ions tween the two compared compounds）.（The m/z values of the parent ions in this figure and the following Fig.6 and Fig.7,showed small errors less than 0.5 Da compared with the values of the corresponding nodes in Fig.3. This difference was produced because the m/z values marked on the nodes in the molecular network are the average m/z values of the precursor ions in a set of mass spectra,and the values in Figs.5-7 are specific values from specific mass spectra）. Compound 5 does not match with butyrolactone I in the molecular network and has no cosine value. However,it is speculated to be an isomer of butyrolactone I through the manual comparison of MS2 spectra

Fig.6 MS2 spectra of compound 2 and its possible derivatives The labeling of compound 2 and 9-10 follows the same numbers as in Fig.3

Fig.7 MS2 spectra of compounds 3,4 and their possible derivatives The labeling of compounds 3,4 and 11-13 follows the same numbers as in Fig.3

Fig.8 Contents of the characteristic products and their derivatives in the metabolites of strain C23-3 under different chemically regulated conditions Groups 1-9：Induction groups added with 3-amino-L-tyrosine（1 mmol/L）,3-hydroxy-L-tyrosine（10 mmol/L）,3-nitro-L-tyrosine（10 mmol/L）,FPP（5 μmol/L）,3,4-dihydroxyphenylpyruvate（1 mmol/L）,farnesol（1 µmol/L）,MSB（10 µmol /L）,H2O2（1 mmol/L）,and L-selenomethionine（61 mmol/L）respectively. The labeling of compounds 1-13 follows the same numbers as in Fig.3. The unit of peak area（area）is counts,counts = CPS*s