<figure><img src="image_32.png" /><figcaption>**FIGURE 19** Proposed mechanisms of dissociation of protonated beauverolide I (m/z 488). Figure adapted from Jegorov et al. (2004).</figcaption></figure>

transfer, complementary product ions are released by the splitting of each protomer complex.

Interestingly, in addition to the **b** series observed from dissociations of the protonated cyclohexadepsipeptide from fungi *Aspergillus ochraceopetaliformis* (vide supra, Figure 14, Hwang et al., 2019), product ions are detected resulting from stepwise processes through internal proton transfer before dissociation. The collision spectrum of the protonated FJ120DPA displays two product ions at *m/z* 503 and *m/z* 233 which are complementary in elemental composition (with one more proton, compared to the protonated precursor, within 2.2 ppm of mass error, Figure 14). Their formation is initiated by the protonated CDP opening either at the NMe amide bond or at the ester bond. Consecutive bond cleavages at either ester or NMe amide bond from both these two isomeric open forms yield before dissociation the intermediate ions that are stabilized by hydrogen bonding between the terminus N-methyl amine of one partner and the terminus oxazolone of the other. They are ion/dipole complexes which dissociate by competitive splitting, into the complementary product *m/z* 503 and *m/z* 233 ions. Such a proton exchange is in favor of the terminus HNMe- group to generate *m/z* 233, while the oxazolone forms the complementary *m/z* 503 ion. Indeed, the proton affinity of the secondary amine is higher than that of oxazolone (Nold et al., 1999). Herein, such a stepwise isomerization into ion/dipole before dissociation of the protonated FJ120DPA does not affect the other dissociation pathways yielding the **b** series through classical processes. However, it is not always the

case since the formation of ion/neutral complexes can hinder all other product ion series, as illustrated by the comparison of the collisional spectra of plitidepsins (vide supra), and their metabolites (Brandon et al., 2005). Especially, the plitidepsin (as a conformer A and B mixture, *m/z* 1110) consists of an exocyclic peptidyl side chain linked to the amino group of the threonine residue included in the ring by its secondary hydroxy group (endocyclic ester linkage) and its carboxylic group giving endocyclic ester and amide linkages, respectively. A second endocyclic ester linkage is introduced with the α-hydroxy-methyl-3-butyric acid (Figure 20A). Under nonresonant excitation conditions, the protonated plitidepsin dissociated mainly through a major pathway, involving cleavage of the exocyclic amide linkage. The peptidyl side chain is then released with a charge distribution at the complementary product ions: (i) the exocyclic peptidyl side chain acylium at *m/z* 295 and (ii) the CDP moiety (*m/z* 817) (Figure 20A). These complementary ions are generated very likely from ion/dipole complex intermediate, although the mobilizable proton transferred to a partner is not generated from the oxazolone or the diketopiperazine nitrogen atoms which do not carry proton. This means that only the proton at the chiral site (the α position of acylium) is mobilizable resulting in a ketene terminal group after its transfer. On the other hand, product ions from the **b** series are not observed as expected. Indeed, NH site, adjacent to the ring-opening position, is absent, so the proton induced dissociation is not possible. From the metabolites of plitidepsin such as the apli-h 1 and 2 congeners (*m/z* 1126),
<figure><img src="image_33.png" /><figcaption>**FIGURE 20** ESI product ion spectra of (A) the protonated and (B) the sodiated plitidepsin A and B mixture from a triple quadrupole instrument. In (A) the cleavage yielding ion/dipole complex is illustrated and (B) the **b** sequence ion is annotated. Figure adapted from Brandon et al. (2005).</figcaption></figure>

their protonated forms are characterized by product ion spectra with similar trends, since only the complementary *m/z* 295 and *m/z* 832 ion pair is detected (Brandon et al., 2005).

Finally, ring-opening and the orientation of subsequent fragmentations are highly dependent on the structure of the CDP, that is, the presence of ester and N-methyl amide bonds, including side chains (considering neighboring groups to endo/exocyclic linkages). As a result, sequences are sometimes difficult to determine, as often certain fragment ion of the **b** series are missed

without obvious reason. In addition, there is an overlap of sequences with different endings defined by competitive cyclic openings, making it difficult to determine the CDP sequence. Comparison of fragmentations with CDPs from the same family is an alternative, although only applicable in special cases. In other words, many structural studies of CDPs based on the dissociation of protonated molecular species are not sufficient. MS/MS of protonated molecules is often combined with NMR analysis to confirm proposed structures. However, for complex mixtures where LC is required, high-resolution
MS/MS is essential. It is therefore desirable to find
molecular species whose dissociations limit ambiguities
by reducing the number of sequences that could overlap.
For this, the study of fragmentation of cationized CDPs
may be a better alternative.

Proposed mechanisms for the dissociation of cationized CDPs provided from a particular specific "in situ derivation". The sodiated CDPs are first naturally generated in the FAB source and now in the ESI source. A long time ago, the mechanism of their dissociations was well documented by Gross's team (Ngoka et al., 1999). They proposed, starting with beauvericin, didemnin B, and enniatin B1 as CDP antibiotics, a peptide sequence approach with reduced sequence overlaps from stepwise pathways. The first step of the process is based on sodium alkoxide salt formation resulting in specific ring-opening of the [M + Na]$^+$ precursor ion with an acylium at one end and at the other, the sodiated alkoxide (NaO-CH) and non-sodiated azanide (NaNH-CH). This can be explained by the fact that the gas phase acidity of the hydroxy group end is higher than that of the primary or secondary amino group end. The resulting open CDPs yield exclusively the **b** series with the alkali retention on the product ions which are induced from the acylium end. At that time, the protonated oxazolone end (Polce et al., 2000; Yalcin et al., 1995) instead of the acylium end was not yet well introduced in the literature. Only more recently the evidence of the formation of protonated oxazolone (or eventually, diketopiperazine) intermediates in place of acylium has been used for the spectral interpretation of protonated CDPs (Jegorov et al., 2004). The protonated site of this 5-membered intermediate, rather than the chiral CH site in the α-position of the acylium end, provides the mobilizable proton needed to promote dissociation of the sodiated CDP and yields the **b** product ion series. Such an opened structure is called a *protonated salt* form (PS) (Colsch et al., 2017; Damont et al., 2019; Darii et al., 2017) in contrast to the *charge-solvated* form (CS) where the ring remains intact and the cation is solvated with the lone pairs of electrons of heteroatoms of CDPs as it occurs with crown ethers (Armentrout, 1999; More et al., 1999) or with ionophores (Bauer et al., 2010; Cruz et al., 2007; Rose & Jenkins, 2007; Suwan et al., 1995) or non-polar amino acids (Cerda & Wesdemiotis, 2000). The sodium alkoxide salt acts as a spectator of the process. When the ion/ion interaction is too weakened by its structural environment, the release of $Na^+$ becomes possible (*vide infra*). In the first study of Nogoka et al., dissociation investigation of three sodiated CDPs (beauvericin, didemnin B, and enniatin B1) were done (Ngoka et al., 1999). From sodiated beauvericin, a covalent trimer

(cyclo[**O**Val-NMePhe]₃, Figure 21A), after ring-opening by an ester bond cleavage, abundant neutrals with *n* residues (1 ≤ *n* ≤ 3) and those weakly abundant with 4 residues, are competitively lost by cleavages of either the ester bond or of the NMe amide linkage.

The behavior of sodiated didemnin B (with peptidyl side chain with amide linkage to threonine) differs and its abundance is roughly 10% of the base peak (ion at *m/z* 943). This product ion corresponds to the ring-opening at the ester bond between Thr and NMeTyrOMe, followed by the NMeTyrOMe loss. The abundance of other product ions is very low (Figure 21B). However, sequential MS³ experiment on the *m/z* 943 leads to abundant product ions due to competitive losses of residues such as: Pro (ion at *m/z* 846), [Pro+H₂O] (*m/z* 828), [Pro+H₂O +Leu] (*m/z* 715). The product ions due to loss of **O**Val residue (*m/z* 577 ion) and water loss at (*m/z* 559) are also abundant. The loss of the α-hydroxyl nonnatural amino acid residue (i.e., isostatine) remains a minor event in MS⁴. The water losses detected from each of the previous product ions are consecutive and originate from the free hydroxy group of the nonnatural amino acid residue. The latter example, the sodiated form of the enniantin B1, cyclo[NMeIle-**O**Val-(NMeVal-**O**Val)₂], dissociates first by competitive ring-opening at the three ester linkages. Each of them results in overlapping **b** series product ions which explains the exclusive presence of doublets separated by 14 *m/z* (Figure 21C). This old study, albeit somewhat forgotten, is still relevant and should have the merit of blazing new trails for structural studies in the CDP field, as the collision spectra of these sodiated molecules are greatly simplified compared to those of protonated molecules. The importance of such an approach has only recently been reported by Li et al. in LC-ESI-MS/MS (Li, He, et al., 2020). The originality of their approach was to combine the product ion spectra of sodiated CDP molecular networks for data treatment. For this purpose, isolated CDPs from *Fusarium* sp. 17-048 (i.e., enniatins A, A1, A2, B, B1, and B4) and from *Beauveria* sp. 186-069 (e.g., beauvericin and analogues) were used. From such networks and low energy collision spectra in nonresonant mode, CDPs present in numerous contaminated food samples could be rapidly characterized. It is also worth noting that the structure of certain isomers of enniatins has been confirmed by NMR. Especially, ¹³C-NMR has enabled us to differentiate NMe Leu from NMe Ile in the case of its congeners (i.e., A, A1, and A4). Despite this resurgence in the use of sodiated CDPs, these cationized forms are not more widely used.

Other differences must be mentioned, especially concerning the specific hydrogen-bonded ion/dipole from plitidepsin A and B (*vide* *supra*, Figure 20A) as intermediate occurring through molecular isomerization
<figure><img src="image_34.png" /><figcaption>**FIGURE 21** ESI product ion spectra of sodiated CDPs: (A) beauvericin (m/z 806), (B) didemnin B (m/z 1134), and (C) enniatin B1 (m/z 676) from ion trap (dotted lines for the ester linkage cleavage for ring opening). Figure adapted from Ngoka et al. (1999).</figcaption></figure>

before dissociation. This stepwise process is hindered by the alkali-cationized plitidepsins and congeners, since such complementary ion pairs are not detected (Figure 20B). This behavior suggests that the approach of the mobile proton to the amide bond of the exocyclic chain linked to the terminal residue with salt will be prevented since this proton will preferentially neutralize negative charge of the neighboring alkoxide part of the

salt, which do not occur from protonated plitidepsin A and B. Thus, this neutralization leads to the release of Na⁺ and the open CDP is therefore lost as a neutral (vide infra). As a result of cleavage in the neighboring linkage of the terminal sodium alkoxide salt (and the polar side chain), the mobilizable proton exothermically neutralizes the salt negative charge, thus releasing the Na⁺ cation. This prevents the formation of small size sodiated **b** fragment
ions i.e., some of the sequence ions are missing from product ion spectra (Brandon et al., 2005). However, in such situation, the observed product ions resulting from dissociations of sodiated (or lithiated) CDPs and protonated CDPs yielding the **b** series are comparable with a *m/z* shift corresponding to the alkali metal cation mass minus the proton mass. Sodiated beauverolides [M+Na]⁺, the tetrapeptides [Leu/Ile-*Hmoa*-Phe-Ala] with the β-hydroxy-4-methyl octanoic acid as *Hmoa*, mainly yield the direct water and Leu/Ile losses with sodium retention (ions [M+Na-H₂O]⁺, **b**₃ and **a**₃) after the ring-opening through ester linkage cleavage between Leu/Ile and the *Hmoa* residue, resulting in the PS form using FTICR (Jegorov et al., 2004). Note that again, the lower size sodiated product ions are not detected although LMCO does not occur with this FTMS instrument. A similar **b**ₙ limit characterizes the dissociation of two minor enniatins (i.e., P1 and P2 with Thr as residue) from *Fusarium* sp. (Uhlig et al., 2009). Their respective sequence is: (i) cyclo[**O**Val-*NMeVal*-*O**Val-*NMe-Thr-*O**Val-*NMeVal*] and (ii) cyclo[**O**Val-*NMeLeu*-*O**Val-*NMeThr-*O**Val-*NMeVal*], with modified residues in bold character. Under resonant excitation conditions using ion trap instrument, ring-opening occurs competitively at the three ester linkages. The loss of water is important due to the presence of Thr residue from which the hydroxy group can be released by mobilizable proton catalysis. In addition, the exclusive loss of the C₃H₈ alkane from enniatin P1 and those of C₃H₈ and C₄H₁₀ from enniatin P2 reflect the presence of the *NMeLeu* residue in addition to *NMeVal*. Even more important is the size of the smallest product ion, corresponding to the **b**₃ ion of each sequence resulting in ring-opening at different ester bonds. This limit is above the *m/z* limit of the resonant mode. Using ion storage experiments, product ion spectrum of the sodiated (and lithiated) enniatin A, cyclo[NMeVal-\-*O**Val**-(Ile-*O**Val*)₂], displays the **b** series up to the **b**₄ product ion (Williams & Brodbelt, 2004). The proposed mechanism of formation of the **b** and **y** series was based on the release of a neutral α-lactams for each step of the sequential MSⁿ experiments. With other alkali-cationized enniatin A, K⁺, and Rb⁺, no information is provided (Williams & Brodbelt, 2004). Note that the alkali-cationized valinomycin dissociates in the same way to provide the **b** series until the **b**₃ product ion (Williams & Brodbelt, 2004). Other metal cations were used, especially Pb²⁺ yielding singly charged enniatin A (by removing one proton) which dissociates by steps of double residues release (Williams & Brodbelt, 2004). Various leaded **b**₁ product ions solvated with H₂O molecule are generated from cationized enniatin A1. A similar behavior was observed from the leaded valinomycin

which gives rise to the formation of **b** and **y** series up to the (b₁ + H₂O) and (y₃ + H₂O) product ions. This differs from leaded lipopeptide such as the iso-surfactin which yields sequence until the **b**₄ and **y**₆ product ions (Williams & Brodbelt, 2004). In all previous studies performed in MSⁿ, the alkali metal cations are retained on product ions of *n*ᵗʰ generation from the product ions of the (*n*−1)ᵗʰ generation until those consisting in 2 or 3 residues and beyond, where the possible release is assumed without evidence.

Interestingly, the observed "product ion cut-off" related to sodiated (or lithiated) product ions with two or three residues (depending on the residue size) must be enlightened. This was not attributed to LMCO of ion trap instrument since for other instruments such as ion beam Qq/TOF and triple quadrupole or Orbitrap-based tandem combined with HCD cell, this residue number limit also characterizes the collisional spectra. A similar behavior characterizes the dissociations of various CDPs such as the enniatin and related species and beauvericin when they are studied (i) by MS/MS through nonresonant excitation in the collision cell of a Qq/TOF instrument (Li, He, et al., 2020) and (ii) by sequential MSⁿ experiments, in resonant excitation mode (Ngoka & Gross, 2000). In all cases, the lowest-size sodiated product ions are made up of two residues.

This "product ion cut-off" seems to be a general trend for the sodiated CDPs and a possible interpretation of this behavior will be explained and discussed below. In addition, the difficulties encountered in obtaining collision spectra of molecules cationized with K⁺ or Rb⁺ need to be explained.

Among the most studied CDPs models are valinomycin, cereulide, and its congeners. Cereulide, cyclo[Ala-*O**Val**-Val-*O**Leu]₃, is analyzed mainly in its alkali-cationized form. This choice of alkali metal cations was motivated by the fact that collision spectra were simplified, since only ester bonds were involved in ring-opening (i.e., cyclo[Ala-*O**Val**-Val-\-*O**Leu**-(Ala-*O**Val**-Val-*O**Leu)₂] and cyclo[Ala--*O**Val**-Val-*O**Leu**-(Ala-*O**Val**-Val-*O**Leu)₂]. This decreases the number of overlapping sequences (with different end residues) consisting only of product ions of the **b** series. As cereulide in solution is an ionophore of the potassium cation, potassiated cereulide was chosen for LC-MS and MS/MS analyses for identification despite the limited sequence described for other potassiated CDPs using mainly ion storage instruments (Marxen, Stark, Frenzel, et al., 2015; Walser et al., 2022). A recent study on collision dissociations of cationized cereulide with alkali metals and ammonium agents was carried out to interpret their product ion spectra (Liuu et al., 2024). Both the resonant and nonresonant excitation modes were used to differentiate the processes taking place along competitive and
consecutive pathways, respectively. To avoid ambiguity, the analysis of the product ions was carried out under high-resolution conditions, using LIT/Orbitrap, Qq/Orbitrap, and Qq/TOF instruments. The use of the Qq/TOF instrument has the advantage of detecting product ions of low *m/z* values (i.e., lower than *m/z* 50) such as Na⁺ (*m/z* 23) or K⁺ (*m/z* 39), not available with the other instruments. However, for that, it is important not to use the default calibration range, but to extend it to include low *m/z* ratios. After this precaution, the product ion spectra can be recorded, revealing the presence of the alkali metal ions formed (Figure 22).

It appears clearly that the product ions of alkali-cationized species are all displayed into ammonium adduct spectrum with a mass shift corresponding to the retention of the alkali metal cation in each of the product ions promoted by mobilizable proton from the PS form. Furthermore, the collision spectra of [M + Li]⁺ and [M + Na]⁺ ions are almost superimposable, with the same low *m/z* limit, which is not the case for [M + K]⁺, which has a “product ion cut-off” at a higher value. This behavior is consistent with the different studies of other CDPs, previously discussed. More to the point is the detection of alkali metal cation as base peak from dissociation of [M + K]⁺ (Bauer et al., 2010; Ducrest et al., 2019; Suwan et al., 1995). Despite this difference, identification continues to be based on the [M + K]⁺ dissociations (Walser et al., 2022). To shed further light on this effect and find its origin, the evolution of collision spectra as a function of

collision energy (i.e., energy-resolved MS, ERMS) was studied, with y-axis abundance in absolute values instead of the usual relative values (Figure 23). Such ERMS breakdown curves allow to better demonstrate the instrumental effect on ion discrimination, that is, the effect on scattering of product ions of low *m/z* (a critical effect on alkali metal ion detection) at higher collision energy. These ERMS were compared according to the alkali metal cation and ammonium-ionized cereulide.

From these ERMS of [M + Li]⁺ and [M + Na]⁺ ions, the evolution of their respective total product ion current without alkali metal ion abundance, TPIC* (and TIC), appears very similar with comparable discrimination of the bare Li⁺ and Na⁺ cations and can be explained from the possible mechanisms as described in Figure 24. This behavior contrasts with that of [M + K]⁺, where the bare K⁺ cation appears at the same time as the first product ions (TPIC* in Figure 23) from the PS form. Furthermore, K⁺ becomes the lone ion at the highest collision energies, which in turn leads to the premature disappearance of the product ions thus explaining the “product ion cut-off.” This clearly means that K⁺ formation comes from (i) small size product ions (within PS form) at the highest energies, and (ii) at the lowest energies, from the intact potassiated cereulide (within CS form). The latter is shown to be provided from dissociation of the CS form, that is, the closed form. In this study, the energy thresholds of Na⁺ and K⁺ are respectively comparable with that of the alkali-cationized

<figure><img src="image_35.png" /><figcaption>**FIGURE 22** ESI product ion spectra of (A) [M + NH₄]⁺, *m/z* 1170 (E<sub>Lab</sub>=60 eV), (B) [M + Li]⁺, *m/z* 1159 (E<sub>Lab</sub> = 94 eV), (C) [M + Na]⁺, *m/z* 1175 (E<sub>Lab</sub> = 94 eV), and (D) [M + K]⁺, *m/z* 1191 (E<sub>Lab</sub> = 94 eV) from Qq/TOF instrument. Each of the product ion series is annotated with a common label color in (B), (C), and (D) respectively shifted by 6.01 *m/z*, 21.98 *m/z*, and 37.96 *m/z* from those assigned to the same series displayed in (A). Figure adapted from Liuu et al. (2024).</figcaption></figure>
<figure><img src="image_36.png" /><figcaption>**FIGURE 23** ERMS breakdown curves of the alkali-cationized cereulide: (A, E) [M + NH₄]⁺ (*m/z* 1170), (B, F) [M + Li]⁺ (*m/z* 1159), (C, G) [M + Na]⁺ (*m/z* 1175), and (D, H) [M + K]⁺ (*m/z* 1191). In (A–D), the profiles are based on the absolute abundances which correspond to (i) total ion current, TIC (◊), (ii) the total product ion current, TPIC or TPIC* with * without alkali metal ion abundance (▲), (iii) the survivor precursor ion current, PIC (■) and (iv) the Na⁺ and K⁺ abundances (●). In (e–h), only detailed profiles of main product ions, including Na⁺ and K⁺, are reported. In (i), to detail the main fragment ion profiles, the K⁺ absolute abundance was limited to 1 × 10⁻⁵ a.u. Experiments were performed under nonresonant excitation conditions using Qq/TOF, with the *m/z* scale calibration adapted for K⁺ and Na⁺ detection and not for that of Li⁺. Figure adapted from Liuu et al. (2024).</figcaption></figure>

12-crown-4-ether (Armentrout, 1999) suggesting that these alkali metal cations are released from the CS forms at the highest energy for Na⁺, and at the lowest energy, for the K⁺ cation.

To conclude, data loss occurs from the potassiated cereulide and its use for cereulide identification should not be recommended, as in addition, sensitivity is lowered due to the role played by the CS form which contributes a
<figure><img src="image_37.png" /><figcaption>**FIGURE 24** Proposed stepwise mechanisms of the alkali-cationized cereulide consisting in: (i) regioselective ring opening at ester linkages yielding the alkali-cationized alkoxide salt at one end and at other a terminus oxazolone, followed by proton transfer either to (ii) amide linkage or (ii') to ester linkage leading to formation of the *b* product ions in the form of either (iii) protonated diketo-morpholine or (iii') protonated oxazolone. Figure adapted from Liuu et al. (2024).</figcaption></figure>

lot to the $[M + K]^+$ ion in contrast to what occurs with the $Na^+$ and $Li^+$ cations which could be the best precursor ions for CDP analysis purposes.

The exploration of the fragmentations of the CDPs should be developed by using other activation techniques such as EID (Cody & Freiser, 1979; Gord et al., 1993), and MAD (Berkout, 2006, 2009; Cook et al., 2009) for singly charged CDPs which give access to electronically excited ion and thus, could provide complementary structural information. Electron-transfer-dissociation can activate doubly and multiply charged positive species by neutralization of one charge. Closely this neutralization, a radical site emerges (i.e., OE ion formation in collision cell) which promotes competitive dissociations of the

adjacent bonds. This dissociation occurring before any energy redistribution, the activation is considered as non-ergotic (Syka et al., 2004). The product ions are injected and then analyzed in linear ion trap analyzer. On the other hand, selected ion activation can occur in the FTICR cell. The precursor ions can be activated by other commercial excitation modes such as IRMPD (*vide supra*) for singly charged and multiply charged species. The doubly (or more) charged positive species can be also activated by electron-capture dissociation (ECD) as applied for valinomycin and beauvericin (Cooper et al., 2004).

Now that a strategy based on high-resolution MS/MS has been developed, particularly in the choice of
molecular species to be activated by collision, it is necessary to describe how to obtain analyzable samples before MS analysis. In other words, it's about how to extract and prepare samples in such a way that they can be identified using methods based on the previous approaches and quantified using regulatory approaches.

## 4 | DETECTION AND QUANTIFICATION OF CDPs BY MS

In parallel to structural characterization, MS detection and quantification of CDPs was implemented in the food safety and pharmaceutical sectors. Sample preparation before the separation and MS analysis is critical for method robustness and its ability to detect trace levels of analytes, notably for CDPs (Andel et al., 2017). This part focuses on the sample preparation protocols used for extraction of the CDPs for MS-based trace analysis, either in food matrices (Table 6) or biofluids (Table 7). We excluded the analysis of CDPs in culture supernatants from producing bacteria, algae, fungus and some marine microorganisms, as well as the sample homogenization and test-portion selection (few grams or a few dozen of microliters for biofluids).

Because of the biological activities of CDPs, detection and/or quantification methods were developed to highlight the presence of toxic CDPs in diverse contaminated food samples or to determine the absorption/distribution/elimination profiles in animals or humans after administration of CDP drug candidates. MS acquisition parameters for detection/quantification of CDPs were derived from the ionization conditions and fragmentation mechanisms already presented above (Section 3.2) and will not be developed further in this section. We illustrated rather the separation techniques and sample preparation protocols implemented to facilitate MS analysis of food and preclinical/clinical matrices. Such matrices contain a high diversity of small molecules, peptides, or proteins, all potentially responsible for deleterious matrix effects for MS-based methods (Cortese et al., 2020).

Separation before MS, whatever the target matrix and the CDPs, were based primarily on reversed-phase LC, to some exception (Berna et al., 1998): the chemistry of the stationary phase varied from $C_6$ to $C_{18}$, with various endcapping, depending on the manufacturer. Most of the separations were performed in gradient mode with mobile phase composition based on water/acetonitrile and/or methanol and other salts or acids adapted to each method to enhance the quality of the separation and of the ionization. Column's dimension, including particle size and the inherent flow rate were adapted to lower the

run time to a few minutes in some studies (Decleer et al., 2016; 2019; Renaud et al., 2017), depending on the analytical system and the maximum acceptable pressure. After LC separation, most of the publications reported positive ionization with ESI, with some exception for APCI (Berna et al., 1998; Uhlig & Ivanova, 2004; Zöllner & Mayer-Helm, 2006) whatever the MS or MS/MS system. Lastly, it is noticeable that some documented methods allowed quick direct analysis without LC separation using direct sample introduction via MALDI sources, both for food or biofluid samples (Ducrest et al., 2019; Wu et al., 2011).

### 4.1 | Detection and quantification of CDPs in food samples

Some *Bacillus cereus* strains produce a small, highly heat-resistant CDP toxin named cereulide. Cereulide is responsible for emetic syndrome in *Bacillus cereus* food-borne outbreaks (Glasset et al., 2016; Rouzeau-Szynalski et al., 2020). Several MS-based methods have been reported to detect or quantify cereulide in food samples since 2002 (Häggblom et al., 2002). For solid-liquid extraction, changes in the solvent extraction protocol were illustrated, using various solvents such as methanol (Zuberovic Muratovic et al., 2014), ethanol (Ducrest et al., 2019), acetonitrile (Biesta-Peters et al., 2010), or ethyl acetate (Yamaguchi et al., 2013), as well as an increasing panel of food matrixes, including milk (Ducrest et al., 2019), rice (Ducrest et al., 2019), french fries or pasta (in't Veld et al. 2019) or some processed food, including baby food (Marxen, Stark, Rütschle, et al., 2015; in't Veld et al. 2019). Solid phase extraction (SPE) was also documented either on normal phase silica with ethylacetate/methanol elution (Yamaguchi et al., 2013) or on reversed $C_{18}$ phase followed by elution with ethanol (Bauer et al., 2010). Note that accelerated solvent extraction was also previously reported with methanol/pentane (Jääskeläinen et al., 2003).

A notable improvement in the robustness of the methods was linked to the introduction of a synthetic stable-isotope labeled $^{13}C_6$-cereulide in the protocol, instead of valinomycin, allowing stable isotope dilution analysis (SIDA), also called isotope dilution assays (IDA), for standardization and quantitative analyses (Bauer et al., 2010; Biesta-Peters et al., 2010; Zuberovic Muratovic et al., 2014; in't Veld et al. 2019). The performance of the MS methods was evaluated during intra-laboratory validation studies. For instance, Muratovic et al. reported precision between 3% to 7% and a limit of quantitation at 1 ng/g in rice and pasta (Zuberovic Muratovic et al., 2014). Interestingly, a study by Veld et al. in 2019
<table><caption>TABLE 6 Summary of the principal steps of extraction protocols, analytical methods and performances for several CDPs in food.</caption><thead><tr><th>Analytes</th><th>Matrix</th><th>Sample extraction</th><th>Column</th><th>Mobile phase composition</th><th>Mass analyser</th></tr></thead><tbody><tr><td>Cereulide</td><td>Bakery products</td><td>- Automatic solid extraction: 100°C, 10 kPa, methanol/pentane (1:1, v/v)<br/>- Evaporation and reconstitution in 1 mL of methanol</td><td>RP-8</td><td>95% Acetonitrile + 4.9% water + 0.1% trifluoroacetic acid</td><td>Ion trap</td></tr><tr><td>Cereulide</td><td>Cooked rice, chinese noodle dish, french fries</td><td>- 50 mL of acetonitrile<br/>- Dilution with valinomycin (IS) and water</td><td>RP-18</td><td>A: Water containing 2% trifluoroacetic acid and 10 mM ammonium acetate<br/>B: Acetonitrile</td><td>TQ</td></tr><tr><td>Cereulide</td><td>Boiled rice and boiled rice supplemented with 10% sunflower oil, milk pudding and liver sausage</td><td>- Addition of <sup>13</sup>C<sub>6</sub>-cereulide<br/>- Extraction with 10 mL ethanol<br/>- C18-SPE, elution by ethanol (1 mL)</td><td>RP-18</td><td>A: Water<br/>B: Methanol</td><td>Q/Trap</td></tr><tr><td>Cereulide</td><td>Milk, cooked and composite food: rice-based food, soybean-based food, noodles, gratin</td><td>- Addition of 2–5 g of anhydrous sodium sulfate<br/>- Extraction twice with 20 mL of ethyl acetate<br/>- Evaporation and reconstitution in ethyl acetate/n-hexane (1:9, v/v),<br/>- SPE on normal-phase silica gel cartridge, elution by 10 mL of ethyl acetate/methanol (9:1, v-v),<br/>- Evaporation and reconstitution in methanol</td><td>RP-8</td><td>A: Water containing 1 mM ammonium formate and 0.1% formic acid<br/>B: Acetonitrile with 0.1% formic acid</td><td>TQ</td></tr><tr><td>Cereulide</td><td>Rice, pasta, and related meals</td><td>- Addition of <sup>13</sup>C<sub>6</sub>-cereulide<br/>- 15 mL of methanol<br/>- Dilution 1:1 in water</td><td>RP-8</td><td>A: Water containing 1 mM ammonium formate and 0.05% formic acid<br/>B: Acetonitrile and 0.05% formic acid</td><td>TQ</td></tr><tr><td>Cereulide</td><td>Rice, milk, and different ready-to-eat meals</td><td>- 1 mL of 75% ethanol<br/>- MALDI matrix: α-cyano-4-hydroxycinnamic acid</td><td>-</td><td>-</td><td>MALDI-TOF</td></tr><tr><td>Cereulide</td><td>Cooked rice, fried rice dish, cream pastry with chocolate, hotdog sausage, mini pancakes, vanilla custard and infant formula</td><td>Extraction based on ISO 18465 with addition of <sup>13</sup>C<sub>6</sub>-cereulide</td><td>RP-18</td><td>A: Water containing 10 mM ammonium formate and 1% trifluoroacetic acid<br/>B: 100% acetonitrile</td><td>Depending of the 11 laboratories (TQ and Ion trap)</td></tr><tr><td>Isocereulides A–G</td><td>Boiled rice, food and feed samples (rice, puddings, desserts, cereals, baby foods, animal feeds) and</td><td>- Addition of <sup>13</sup>C<sub>6</sub>-cereulide<br/>- Extraction with 3 mL of acetonitrile</td><td>RP-18</td><td>A: Water containing 10 mM ammonium formate and 0.1% formic acid</td><td>TQ</td></tr></tbody></table>
<table><thead><tr><th>LOQ</th><th>LOD</th><th>Range</th><th>Recovery</th><th>Intra day-repetability</th><th>Inter-day precision</th><th>Reference</th></tr></thead><tbody><tr><td>50 ng/g</td><td>-</td><td>50-500 ng/g</td><td>&gt;70%</td><td>-</td><td>&lt;30%</td><td>Jääskeläinen et al. (2003)</td></tr><tr><td>4 µg/kg</td><td>-</td><td>4-100 µg/kg</td><td>97%-107%</td><td>2%-5%</td><td>2%-6%</td><td>Biesta-Peters et al. (2010)</td></tr><tr><td>30-50 ng/g rice/rice with oil</td><td>3-5 ng/g rice/rice with oil</td><td>1-100 ng/mL in solvent</td><td>104%-111%</td><td>-</td><td>-</td><td>Bauer et al. (2010)</td></tr><tr><td>0.5 ng/mL</td><td>0.1 ng/mL</td><td>0.0035-63 µg/g</td><td>67%-107%</td><td>-</td><td>&lt;10%</td><td>Yamaguchi et al. (2013)</td></tr><tr><td>1 ng/g</td><td>0.1 ng/g</td><td>1-500 ng/g</td><td>91-93%</td><td>-</td><td>3%-7%</td><td>Zuberovic Muratovic et al. (2014)</td></tr><tr><td></td><td>30 pg/mL</td><td>-</td><td>-</td><td>-</td><td>-</td><td>Ducrest et al. (2019)</td></tr><tr><td>Below 1 µg/kg</td><td>-</td><td>1-99 µg/kg</td><td>96.5% for mini pancakes to 99.3% for fried rice dish</td><td>Maximum 14%</td><td>Maximum 24%</td><td>in't Veld et al. (2019)</td></tr><tr><td>0.05 ng/g</td><td>0.1 ng/g</td><td>0.04-20 ng/mL in solvent</td><td>110%-114%</td><td>1%-3%</td><td>2%-8%</td><td>Marxen, Stark, Rütschle, et al. (2015)</td></tr></tbody></table>

(Continues)
<table><caption>TABLE 6 (Continued)</caption><thead><tr><th>Analytes</th><th>Matrix</th><th>Sample extraction</th><th>Column</th><th>Mobile phase composition</th><th>Mass analyser</th></tr></thead><tbody><tr><td></td><td>two suspicious noodle samples</td><td></td><td></td><td>B: Acetonitrile/water (85:15, v/v) containing 0.25% formic acid</td><td></td></tr><tr><td>Cereulide, beauvericin and enniatins A, A1, B and B1</td><td>Maize, wheat, pasta, and rice</td><td>— Extraction with acetonitrile/water (84:16 v/v) for all matrices except for rice 100% methanol<br/>— Evaporation and reconstitution in initial mobile phase composition</td><td>RP-18</td><td>A: Water/acetonitrile/methanol (95:4:1, v/v/v) containing 1 mM ammonium formate and 0.3% formic acid,<br/>B: Acetonitrile/methanol/water (78:20:2, v/v/v) containing 1 mM ammonium formate and 0.3% formic acid</td><td>TQ</td></tr><tr><td>Beauvericin (BEA) and enniatins (ENNs) A, A1, B and B1</td><td>Oats, wheat and barley grains</td><td>80 mL of acetonitrile/water (84:16, v/v)</td><td>RP-18</td><td>Water/methanol/acetonitrile (15:40:45, v/v/v) containing 15 mM ammonium formate</td><td>Ion trap</td></tr><tr><td>Beauvericin and enniatins A, A1, B and B1</td><td>Maize</td><td>160 mL of acetonitrile/water (84:16, v/v)</td><td>RP-6</td><td>A: Water<br/>B: Acetonitrile</td><td>TQ</td></tr><tr><td>Beauvericin and enniatins A, A1, B and B1</td><td>Wheat grains and Maize</td><td>— 2 mL solvent mixture (acetonitrile/water/acetic acid, 79:20:1, v/v/v)<br/>— Dilution 1:2 same solvent</td><td>RP-18</td><td>A: Methanol/water/acetic acid (10:89:1, v/v/v) containing 5 mM ammonium acetate<br/>B: Methanol/water/acetic acid (97:2:1, v/v/v) containing 5 mM ammonium acetate</td><td>Q/Trap</td></tr><tr><td>Enniatins and bassianolides</td><td>Maize, haylage, barley, and mixed silage</td><td>— Lyophilization<br/>— Extraction with (acetonitrile/water/acetic acid, 79:20:1, v/v/v) between 3 and 16 mL dilution 1:1 with the same solvent</td><td>RP-8</td><td>A: Water containing 0.1% formic acid<br/>B: Acetonitrile containing 0.1% formic acid</td><td>Ion trap</td></tr><tr><td>Beauvericin and enniatins A, A1, B, and B1</td><td>Milk</td><td>— 10 mL of acidified acetonitrile (0.5% formic acid)<br/>— Addition of QuEChERS salts (8 g of MgSO<sub>4</sub> and 1.2 g of NaCl)<br/>— Evaporation of 1 mL of supernatant and reconstitution in acetonitrile/water/acetic acid (49:50:1, v/v/v)</td><td>RP-18</td><td>A: water containing 0.1% formic acid and 5 mM ammonium formate<br/>B: methanol</td><td>TQ</td></tr></tbody></table>

Abbreviations: BEA, beauvericin; ENN, enniatin; IS, internal standard.
<table><thead><tr><th>LOQ</th><th>LOD</th><th>Range</th><th>Recovery</th><th>Intra day-repetability</th><th>Inter-day precision</th><th>Reference</th></tr></thead><tbody><tr><td>0.3-2.9 µg/kg</td><td>0.1-1.0 µg/kg</td><td>2-400 µg/kg</td><td>84%-106%</td><td>2%-20%</td><td>3%-20%</td><td>Decleer et al. (2016); (2019)</td></tr><tr><td>10-13 µg/kg</td><td>3.0-4 µg/kg</td><td>- BEA: 8-512 µg/kg<br>- ENNA 3-30 µg/kg<br>- ENNA1: 8-160 µg/kg<br>- ENNB: 8-152 µg/kg<br>- ENNB1: 14-432 µg/kg</td><td>- BEA: 115%<br>- ENNs:<br>80%-104%</td><td>-</td><td>Mainly &lt;25%</td><td>Uhlig and Ivanova (2004)</td></tr><tr><td>- BEA: 13 ng/g<br>- ENNs:<br>17-37 ng/g</td><td>-</td><td>- BEA: 13-800 µg/kg<br>- ENNs 17-1000 µg/kg</td><td>- BEA: 96%-104%<br>- ENNs:<br>91%-110%</td><td>-</td><td>8-26%</td><td>Sørensen et al. (2008)</td></tr><tr><td>- BEA 3-4 µg/kg<br>- ENNs &lt;1 µg/kg<br>in maize (not validated in wheat)</td><td>-</td><td>- LOQ to 48-864 µg/kg for ENNs<br>- LOQ to 800 µg/kg for BEA in maize<br>- LOQ to 80 µg/kg for BEA in wheat</td><td>94%-106%</td><td>-</td><td>&lt;2%</td><td>Sulyok et al. (2006); Suchowilska et al. (2010)</td></tr><tr><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td>Renaud et al. (2017)</td></tr><tr><td>- BEA: 1.95 µg/L<br>- ENNs:<br>0.08-0.37 µg/L</td><td>- BEA: 0.59 µg/L<br>- ENNs:<br>0.02-0.11 µg/L</td><td>- BEA: 3.12-200 µg/L<br>- ENNs: 0.78-200 µg/L</td><td>- BEA: 91%-100%<br>- ENNs: 86%-120%</td><td>- BEA: 4%<br>- ENNs: max 5%</td><td>- BEA: 7%<br>- ENNs:<br>max 8%</td><td>González-Jartín et al. (2021)</td></tr></tbody></table>
<table><caption>TABLE 7 Summary of the principal steps of extraction protocols, analytical methods and performances for several CDPs in biofluids.</caption><thead><tr><th>Analytes</th><th>Matrix</th><th>Sample extraction</th><th>Column</th><th>Mobile phase composition</th><th>Mass analyser</th></tr></thead><tbody><tr><td>Enniatin B (ENNB) and Beauvericin (BEA)</td><td>Mice urine and serum</td><td>1.5 mL of acetonitrile</td><td>RP-18</td><td>A: methanol/water/acetic acid (10:89:1, v/v/v) containing 5 mM ammonium acetate<br>B: methanol/water/acetic acid (97/2/1, v/v/v) containing 5 mM ammonium acetate</td><td>Q/Trap</td></tr><tr><td>Cereulide</td><td>Porcine urine and plasma</td><td>- Ethanol, volume depending on weight 10–40 mL<br>- Dilution 1:5 in water<br>- C18-SPE, elution with 2,5 mL of ethanol</td><td>RP-18</td><td>A: water<br>B: methanol</td><td>Q/Trap</td></tr><tr><td>Largazole thiol</td><td>human or rat plasma</td><td>- 1mL ethyl acetate<br>- addition of harmine, as IS<br>- Evaporation and reconstitution in 200 µL of methanol/water (60:40 v/v) acidified with 0.1% of formic acid</td><td>RP-8</td><td>A: water containing 0.1% of formic acid<br>B: methanol containing 0.1% of formic acid</td><td>TQ</td></tr><tr><td>LY355703</td><td>Dog and Mouse Plasma</td><td>- Addition of LY354504 as IS<br>- 200 µL of acetonitrile<br>- Addition of 1 mL of water<br>- C18-SPE, elution with 1 mL of acetonitrile<br>- Evaporation of the supernatant and reconstitution in water/acetonitrile/propan-2-ol (50:45:5, v/v/v)</td><td>HP-cyano</td><td>acetonitrile/water/propan-2-ol (63:30:7, v/v/v)</td><td>TQ</td></tr><tr><td>Plitidepsin (Aplidin*)</td><td>Human plasma, whole blood, and urine</td><td>- Addition of didemnin B (IS)<br>- 2 mL acetonitrile containing 1% formic acid.<br>- 2 mL of chloroform<br>- Evaporation of the supernatant and reconstitution in water/acetonitrile/formic acid (49.5:49.5:1, v/v/v)</td><td>RP-18</td><td>A: water containing 0.5% of formic acid<br>B: acetonitrile containing 0.5% of formic acid</td><td>TQ</td></tr><tr><td>Plitidepsin (Aplidin*)</td><td>Human plasma, whole blood, and urine</td><td>- Extraction under basic condition (1 M aqueous ammonia) with TBME<br>- Evaporation and reconstitution in acetonitrile/water (50:50, v/v) containing formic acid</td><td>RP-18</td><td>A: water containing 0.1% formic acid and 5 mM ammonium acetate<br>B: acetonitrile containing 0.1% formic acid</td><td>TQ</td></tr><tr><td>Romidepsin FK228</td><td>Human and mouse plasma</td><td>- 1.6 mL ethyl acetate<br>- Addition of harmine (IS)<br>- Evaporation of the supernatant and reconstitution in 50 µL of methanol/ 0.2% formic acid (55:45, v/v)</td><td>RP-18</td><td>A: water containing 0.2% of formic acid<br>B: methanol containing 0.2% of formic acid</td><td>Q</td></tr><tr><td>Valinomycin</td><td>Soybean, urine and plasma</td><td>- Soybean: 500 mL of water/ethanol (40:60, v/v)<br>- Nanoparticles based microextraction</td><td>-</td><td>-</td><td>MALDI-TOF</td></tr><tr><td>Valinomycin</td><td>Human urine and plasma</td><td>- 2 µL of organic octanol<br>- 1 µL of microdroplet contact at 240 rpm, 5 min<br>- MALDI Matrix: α-cyano-4-hydroxycinnamic acid</td><td>-</td><td>-</td><td>MALDI-TOF</td></tr></tbody></table>

Abbreviations: BEA, beauvericin; ENN, enniatin; IS, internal standard.
<table><thead><tr><th>LOQ</th><th>LOD</th><th>range</th><th>recovery</th><th>intra day-repetability</th><th>inter-day precision</th><th>Reference</th></tr></thead><tbody><tr><td>BEA: 0.15 µg/kg urine and 0.10 µg/kg Serum</td><td>-</td><td>0.01-100 µg/L in solvent</td><td>BEA: 85-90% ENNB: 88-95%</td><td>&lt;8%</td><td>&lt;14%</td><td>Rodríguez-Carrasco et al. (2016)</td></tr><tr><td>ENNB: 0.10 µg/kg urine and 0.05 µg/kg serum</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td>Bauer et al. (2018)</td></tr><tr><td>12.5 ng/mL</td><td>-</td><td>12.5-400 ng/mL</td><td>101-106%</td><td>7-13%</td><td>7-10%</td><td>Yu et al. (2014)</td></tr><tr><td>2 ng/mL</td><td>-</td><td>2-530 ng/mL</td><td>84-107%</td><td>&lt;9%</td><td>&lt;8%</td><td>Berna et al. (1998)</td></tr><tr><td>1 ng/mL</td><td>0.25 ng/</td><td>1-200 or 250 ng/mL</td><td>46-60%</td><td></td><td>&lt;16%</td><td>Celli et al. (2004)</td></tr><tr><td>0.1 ng/mL</td><td>-</td><td>0.1-100 ng/mL</td><td>&gt;90%</td><td></td><td>&lt;6%</td><td>Andel et al. (2017)</td></tr><tr><td>2 ng/mL</td><td></td><td>2-1000 ng/mL</td><td>Human plasma: 101.5% to 106.4%</td><td>0.6-4%</td><td>0.6-7%</td><td>Chen et al. (2008)</td></tr><tr><td>20-68 nM</td><td></td><td>0.2-1.0 M</td><td></td><td></td><td></td><td>Kailasa &amp; Wu (2010)</td></tr><tr><td>120 nM to 170 nM</td><td></td><td>0.5-2.5 mM</td><td></td><td></td><td></td><td>Wu et al. (2011)</td></tr></tbody></table>
reported the inter-laboratory evaluation of a method using acetonitrile extraction (in't Veld et al. 2019), ¹³C₆-cereulide as internal standard counterbalancing any matrix effects and multiple reaction monitoring (MRM) quantitation of cereulide in diverse samples (e.g., cooked rice, cream, sausage, pancakes, and infant formula). Results from the 11 participating laboratories showed quantitation level below 1 ng/g, excepted for one laboratory, good recoveries (from 96.5% to 98.3%), repeatability and reproducibility of the method with maximum CV at 14% and 24%, although different MS instruments were used. This method was standardized under the EN ISO 18465 reference.

The structural diversity of cereulide was recently considered. A new quantitative method was established for cereulide and seven isocereulide variants (A-G). The method was validated in several food types: after acetonitrile extraction, quantification limits reached 0.5 ng/g with recoveries between 100% and 114% and good reported inter-day precision. Isocereulides A to G were identified and quantified in two suspicious noodle samples, up to 268 ng/g, cereulide being predominant with 6198 ng/g (Marxen, Stark, Rütschle, et al., 2015).

Other CDPs are of particular concern in the food sector. Beauvericin, enniatins, destruxins and bassianolides belong to the family of mycotoxins and are produced by fungi. Similar extraction methods to cereulide were reported, using solvent extraction with water and acetonitrile acidified or not (Decleer et al., 2016; 2019; Sorensen et al., 2008; Suchowilska et al., 2010; Sulyok et al., 2006), or the more recent so-called QuEChERS protocol (quick, easy, cheap, effective, rugged, and safe) (González-Jartín et al., 2021; Koike et al., 2024), commonly used for pesticides analysis in food. With such protocol for multi-toxins analysis in milk or fried rice, the extraction step with acetonitrile is followed by a liquid-liquid partitioning (demixion) resulting from the addition of inorganic salts. In this way, the polar components of the matrix remain in the aqueous layer leading to an extract suitable for MS analysis. For the toxins studied in milk, a second step of dispersive SPE clean-up induced a reduction of recoveries due to adsorption on the C₁₈ media and was thus abandoned.

## 4.2 | Detection and quantification of CDPs in animal or human biofluids

Bioanalytical methods for clinical or preclinical studies require careful validation according to the regulations applicable when evaluating drug candidates (Moein et al., 2017). Accuracy and precision of the methods reported for CDPs were established with quality controls

and met the requirements for bioanalytical assays, ranging between 85% and 115% and ± 15%, respectively.

The antitumor activity of selected CDPs (i.e., romidepsin FK228, plitidepsin commercialized under "Aplidin" name) led to pharmaceutical evaluation as anticancer drug candidates (Andel et al., 2017; Celli et al., 2004; Chen et al., 2008). After administration to animals or humans, measurements of circulating concentrations were required to determine the drug candidates' pharmacokinetic properties. To this aim, MS-based methods were developed for the absolute quantification of CDPs in animal or human biofluids. After extraction of the CDPs, quantification was achieved mainly by reverse phase liquid-chromatography (RP-LC) coupled with single or MS/MS operated in MRM mode (Andel et al., 2017; Yu et al., 2014). Absolute quantification of the CDP levels was achieved by spiking a blank matrix with a standard solution of the CDPs and a stable isotopically labeled version, when available, used as an internal standard to compensate for the matrix effect (Andel et al., 2017).

Protocols for extracting CDPs from plasma or urine showed differences with the food safety sector. Usual approaches in bioanalytical laboratories were used, including precipitation/extraction of plasma/blood protein by organic solvents (Berna et al., 1998), liquid/liquid extraction (LLE) with organic solvent of different polarities: ethylacetate (Yu et al., 2014), methyl tert-butyl ether (Chen et al., 2008), chloroform (Celli et al., 2004) or ethanol, eventually followed by SPE on a C₁₈ cartridge (Bauer et al., 2018) or a combination thereof (Berna et al., 1998). For instance, van Angel et al. combined protein precipitation under basic condition and LLE for ptilidepsin quantitation in urine, human plasma, or whole blood down to 0.1 ng (Andel et al., 2017). Kailasa et al. reported an original protocol for valinomycin based on functionalized Ag₂Se nanoparticles as effective extracting probes. A limit of detection (LOD) down to 20 nM was reached, and clean mass spectra were obtained by MALDI-MS, even in plasma or urine samples (Kailasa & Wu, 2010). This antibiotic was also originally determined in urine and plasma by single drop micro-extraction followed by MALDI-MS analysis reaching comparable detection limits (120 nM) (Wu et al., 2011).

Cereulide distribution was also studied in porcine urine and plasma, via ethanolic LLE followed by a C₁₈-SPE despite no method performance are described (Bauer et al., 2018). Regarding mycotoxin determination in biological samples, they were the subject of two reviews referring to LC-API/MS or HRMS (Arroyo-Manzanares et al., 2021; Zöllner & Mayer-Helm, 2006). Interestingly, the distribution of enniatin B and Beauvericin as potential anticancer drugs were investigated in mice urine and serum by acetonitrile extraction followed
by MS analysis on a Q/Trap instrument with recoveries above 85% (Rodríguez-Carrasco et al., 2016).

5 | CONCLUSION AND OUTLOOK

Precise structural characterization of CDPs is essential for a comprehensive understanding of their biological and functional properties. NMR methods were used for a long time to obtain thorough structural characterization of CDPs, including insight into their stereochemistry and conformation, and were sometimes limited by their intrinsic low sensitivity. The limitations of these approaches were remedied by using MS-based ones. Although GC-EIMS methods proved relevant in obtaining insight into the nature and branching of the different building blocks constituting CDPs, ESI-HRMS exhibited an unsurpassed ability to resolve their structural make up in a straightforward manner. Low energy fragmentation of adduct species (e.g., [M + Na]⁺, [M + Li]⁺ and less [M + K]⁺) of CDPs desorbed under ESI conditions also provides valuable and easy-to-interpret product ion spectra that allow CDP sequencing. Contrary to the expectations based on state-of-the-art techniques mentioned in the introduction, the use of alkali-cationized CDPs, and in particular the sodiated ones, makes the structural study of CDPs easier than the analysis of cyclopeptides. Indeed, unlike cationized cyclopeptides are essentially in *charged solvated* form, resulting in very little ring fragmentation, sodiated CDPs, mainly in *protonated salt* forms, allow mobile proton-induced cleavage of the covalent bond after regioselective ring-opening at the ester bond, to give the **b** series product ions.

Interestingly, some of these MS-based methods were combined with efficient chromatographic separations and sample preparation protocols for quantitative applications in a diversity of matrices from the food safety and pharmaceutical sectors.

Although powerful, such ESI-HRMS/MS strategies do not elucidate CDP's conformation and stereochemistry. In the future, strategies based on alternative fragmentation methods, such as those based on electron attachment or capture, could become effective additional tools for achieving this goal. Also, combining HRMS(/MS) with ion mobility spectrometry should facilitate separation of CDP (stereo)isomers and therefore holds great promise for gathering the different structural layers of information required to explore and better understand the huge chemical and functional diversity of naturally occurring CDPs.

AUTHOR CONTRIBUTIONS

**Sophie Liuu:** Conceptualization; supervision; visualization; writing—original draft; writing—review and

editing. **Annelaure Damont:** Writing—original draft; writing—review and editing. **Alain Perret:** Writing—original draft; writing—review and editing. **Olivier Firmesse:** Writing—original draft; writing—review and editing. **François Becher:** Writing—original draft; writing—review and editing. **Gwenaëlle Lavison-Bompard:** Writing—original draft; writing—review and editing. **Amandine Hueber:** Writing—original draft; writing—review and editing. **Amina S Woods:** Writing—original draft; writing—review and editing. **Ekaterina Darii:** Writing—original draft; writing—review and editing. **François Fenaille:** Writing—original draft; writing—review and editing. **Jean-Claude Tabet:** Conceptualization; writing—original draft; writing—review and editing.

ORCID

Sophie Liuu ID http://orcid.org/0009-0009-7269-4463

Annelaure Damont ID https://orcid.org/0000-0003-4075-5187

Alain Perret ID https://orcid.org/0000-0002-8896-1978

Olivier Firmesse ID http://orcid.org/0000-0003-2415-2802

François Becher ID https://orcid.org/0000-0002-1075-9980

Gwenaëlle Lavison-Bompard ID https://orcid.org/0000-0001-6793-6290

Amandine Hueber ID https://orcid.org/0009-0009-0800-5774

Amina S. Woods ID https://orcid.org/0000-0002-9716-345X

Ekaterina Darii ID https://orcid.org/0000-0001-7129-8842

François Fenaille ID https://orcid.org/0000-0001-6787-4149

Jean-Claude Tabet ID https://orcid.org/0000-0003-0080-2946

REFERENCES

Afonso, Carlos, Richard B. Cole, and Jean-Claude Tabet. 2010. "Dissociation of Even-Electron Ions." In *Electrospray and MALDI Mass Spectrometry*, 631–682. John Wiley & Sons, Ltd. https://doi.org/10.1002/9780470588901.ch17.

Agrawal, Shivankar, Alok Adholeya, and Sunil K. Deshmukh. 2016. "The Pharmacological Potential of Non-Ribosomal Peptides from Marine Sponge and Tunicates." *Frontiers in Pharmacology* 7: 333. https://www.frontiersin.org/articles/10.3389/fphar.2016.00333.

Almaliti, Jehad, Karla L. Malloy, Evgenia Glukhov, Carmenza Spadafora, Marcelino Gutiérrez, and William H. Gerwick. 2017. "Dudawalamides A–D, Antiparasitic Cyclic Depsipeptides from the Marine Cyanobacterium Moorea Producens." *Journal of Natural Products* 80 (6): 1827–1836. https://doi.org/10.1021/acs.jnatprod.7b00034.

Alonzo, Diego A., and T. Martin Schmeing. 2020. "Biosynthesis of Depsipeptides, or Depsi: The Peptides with Varied Generations." *Protein Science* 29 (12): 2316–2347. https://doi.org/10.1002/pro.3979.
Amagata, Taro, Brandon I. Morinaka, Akiko Amagata, Karen Tenney, Frederick A. Valeriote, Emil Lobkovsky, Jon Clardy, and Phillip Crews. 2006. "A Chemical Study of Cyclic Depsipeptides Produced by a Sponge-Derived Fungus." *Journal of Natural Products* 69 (11): 1560–1565. https://doi.org/10.1021/np060178k.

van Andel, L., H. Rosing, S. Fudio, P. Avilés, M. M. Tibben, A. Gebretensae, J. H. M. Schellens, and J. H. Beijnen. 2017. "Liquid Chromatography-Tandem Mass Spectrometry Assay to Quantify Plitidepsin in Human Plasma, Whole Blood and Urine." *Journal of Pharmaceutical and Biomedical Analysis* 145:137–143. https://doi.org/10.1016/j.jpba.2017.06.013.

Armentrout, P. B. 1999. "Cation–Ether Complexes in the Gas Phase: Thermodynamic Insight into Molecular Recognition." *International Journal of Mass Spectrometry* 193 (2): 227–240. https://doi.org/10.1016/S1387-3806(99)00165-7.

Arpino, Patrick. 1992. "Combined Liquid Chromatography Mass Spectrometry. Part III. Applications of Thermospray." *Mass Spectrometry Reviews* 11 (1): 3–40. https://doi.org/10.1002/ mas.1280110103.

Arroyo-Manzanares, Natalia, Natalia Campillo, Ignacio López-García, Manuel Hernández-Córdoba, and Pilar Viñas. 2021. "High-Resolution Mass Spectrometry for the Determination of Mycotoxins in Biological Samples. A Review." *Microchemical Journal* 166:106197. https://doi.org/10.1016/j.microc.2021. 106197.

Avan, Ilker, C. Dennis Hall, and Alan R. Katritzky. 2014. "Peptidomimetics via Modifications of Amino Acids and Peptide Bonds." *Chemical Society Reviews* 43 (10): 3575–3594. https:// doi.org/10.1039/C3CS60384A.

Awazu, Naoyuki, Katsushige Ikai, Junko Yamamoto, Kazuko Nishimura, Shigetoshi Mizutani, Kazutoh Takesako, and Ikunoshin Kato. 1995. "Structures and Antifungal Activities of New Aureobasidins." *The Journal of Antibiotics* 48 (6): 525–527. https://doi.org/10.7164/antibiotics.48.525.

Banerjee, Raja, S. Sudarslal, R. S. Ranganayaki, and S. Raghothama. 2011. "Effect of Ester Chemical Structure and Peptide Bond Conformation in Fragmentation Pathways of Differently Metal Cationized Cyclodepsipeptides." *Organic & Biomolecular Chemistry* 9 (18): 6234–6245. https://doi.org/10.1039/ C1OB05392B.

Barbacci, Damon, Shelley N. Jackson, Ludovic Muller, Thomas Egan, Ernest K. Lewis, J. Albert Schultz, and Amina S. Woods. 2012. "Cellular Membrane Phospholipids Act as a Depository for Quaternary Amine Containing Drugs Thus Competing with the Acetylcholine/Nicotinic Receptor." *Journal of Proteome Research* 11 (6): 3382–3389. https://doi.org/10. 1021/pr300184g.

Bauer, Tobias, Wolfgang Sipos, Timo D. Stark, Tobias Käser, Christian Knecht, Rene Brunthaler, Armin Saalmüller, Thomas Hofmann, and Monika Ehling-Schulz. 2018. "First Insights Into Within Host Translocation of the Bacillus Cereus Toxin Cereulide Using a Porcine Model." *Frontiers in Microbiology* 9:2652. https://www.frontiersin.org/articles/10. 3389/fmicb.2018.02652.

Bauer, Tobias, Timo Stark, Thomas Hofmann, and Monika Ehling-Schulz. 2010. "Development of a Stable Isotope Dilution Analysis for the Quantification of the Bacillus Cereus Toxin Cereulide in Foods." *Journal of Agricultural and Food

*Chemistry* 58 (3): 1420–1428. https://doi.org/10.1021/ jf9033046.

Beckey, H. D. 1977. "1 - Theory of field ionization (FI) and field desorption (FD)." In Principles of Field Ionization and Field Desorption Mass Spectrometry, edited by H. D. Beckey, 1–25. International Series of Monographs on Analytical Chemistry. Pergamon. https://doi.org/10.1016/B978-0-08-020612-7. 50006-8.

Belofsky, Gilbert N, Paul R Jensen, and William Fenical. 1999. "Sansalvamide: A New Cytotoxic Cyclic Depsipeptide Produced by a Marine Fungus of the Genus Fusarium." *Tetrahedron Letters* 40 (15): 2913–2916. https://doi.org/10. 1016/S0040-4039(99)00393-7.

Benninghoven, A., D. Jaspers, and W. Sichtermann. 1976. "Secondary-Ion Emission of Amino Acids." *Applied Physics* 11 (1): 35–39. https://doi.org/10.1007/BF00895013.

Berkout, Vadym D. 2006. "Fragmentation of Protonated Peptide Ions via Interaction with Metastable Atoms." *Analytical Chemistry* 78 (9): 3055–3061. https://doi.org/10.1021/ ac060069a.

Berkout, Vadym D. 2009. "Fragmentation of Singly Protonated Peptides via Interaction with Metastable Rare Gas Atoms." *Analytical Chemistry* 81 (2): 725–731. https://doi.org/10.1021/ ac802214e.

Berna, M., R. Shugert, and J. Mullen. 1998. "Determination of LY355703 in Dog and Mouse Plasma by Positive Ion Liquid Chromatography/Tandem Mass Spectrometry with Atmospheric Pressure Chemical Ionization." *Journal of Mass Spectrometry* 33 (2): 138–143. https://doi.org/10.1002/(SICI) 1096-9888(199802)33:2<138::AID-JMS617>3.0.CO;2-7.

Bertaud, W. S., M. C. Probine, J. S. Shannon, and A. Taylor. 1965. "Isolation of a New Depsipeptide from Pithomyces Chartarum." *Tetrahedron* 21 (2): 677–680. https://doi.org/10.1016/ S0040-4020(01)82239-0.

Biemann, Klaus. 1988. "Contributions of Mass Spectrometry to Peptide and Protein Structure." *Biomedical & Environmental Mass Spectrometry* 16 (1–12): 99–111. https://doi.org/10.1002/ bms.1200160119.

Biesta-Peters, Elisabeth G., Martine W. Reij, Richard H. Blaauw, Paul H. In't Veld, Andreja Rajkovic, Monika Ehling-Schulz, and Tjakko Abee. 2010. "Quantification of the Emetic Toxin Cereulide in Food Products by Liquid Chromatography-Mass Spectrometry Using Synthetic Cereulide as a Standard." *Applied and Environmental Microbiology* 76 (22): 7466–7472. https://doi.org/10.1128/AEM.01659-10.

Boudreau, Paul D., Tara Byrum, Wei-Ting Liu, Pieter C. Dorrestein, and William H. Gerwick. 2012. "Viequeamide A, a Cytotoxic Member of the Kulolide Superfamily of Cyclic Depsipeptides from a Marine Button Cyanobacterium." *Journal of Natural Products* 75 (9): 1560–1570. https://doi.org/10.1021/ np300321b.

Brandon, Esther F. A., Ronald D. van Ooijen, Rolf W. Sparidans, Luis López Lázaro, Albert J. R. Heck, Jos H. Beijnen, and Jan H. M. Schellens. 2005. "Structure Elucidation of Aplidine Metabolites Formed in Vitro by Human Liver Microsomes Using Triple Quadrupole Mass Spectrometry." *Journal of Mass Spectrometry* 40 (6): 821–831. https://doi.org/10.1002/jms.863.

Broberg, Anders, Audrius Menkis, and Rimvydas Vasiliauskas. 2006. "Kutznerides 1–4, Depsipeptides from the Actinomycete
Kutzneria Sp. 744 Inhabiting Mycorrhizal Roots of Picea Abies Seedlings." *Journal of Natural Products* 69 (1): 97-102. https://doi.org/10.1021/np050378g.

Budzikiewicz, Herbert, Carl Djerassi, and Dudley H. Williams. 1964. *Interpretation of Mass Spectra of Organic Compounds*. Holden-Day.

Bughin, Carine, Géraldine Masson, and Jieping Zhu. 2007. "Rapid Synthesis of Cyclodepsipeptides Containing a Sugar Amino Acid or a Sugar Amino Alcohol by a Sequence of a Multi-component Reaction and Acid-Mediated Macrocyclization." *The Journal of Organic Chemistry* 72 (5): 1826-1829. https://doi.org/10.1021/jo0621874.

Burja, Adam M., Bernard Banaigs, Eliane Abou-Mansour, J. Grant Burgess, and Phillip C. Wright. 2001. "Marine Cyanobacteria—A Prolific Source of Natural Products." *Tetrahedron* 57 (46): 9347-9377. https://doi.org/10.1016/S0040-4020(01)00931-0.

Burmeister, H. R., R. F. Vesonder, R. E. Peterson, and C. E. Costello. 1985. "Production and Purification of a Peptide of Fusarium Tricinctum That Causes Conidia of Penicillium to Swell." *Mycopathologia* 91 (1): 53-56. https://doi.org/10.1007/BF00437288.

Butt, Tariq M., Noomen Ben El Hadj, Anke Skrobek, Willem J. Ravensberg, Chengshu Wang, Catherine M. Lange, Alain Vey, Umi-Kulsoom Shah, and Ed Dudley. 2009. "Mass Spectrometry as a Tool for the Selective Profiling of Destruxins; Their First Identification in Lecanicillium Longisporum." *Rapid Communications in Mass Spectrometry* 23 (10): 1426-1434. https://doi.org/10.1002/rcm.4018.

Byeon, Hye-Eun, Bong-Kyun Park, Joung Han Yim, Hong Kum Lee, Eun-Yi Moon, Dong-Kwon Rhee, and Suhkneung Pyo. 2012. "Stereocalpin A Inhibits the Expression of Adhesion Molecules in Activated Vascular Smooth Muscle Cells." *International Immunopharmacology* 12 (2): 315-325. https://doi.org/10.1016/j.intimp.2011.11.020.

Byhell, Benjamin J., Sándor Suhai, Arpád Somogyi, and Béla Paizs. 2009. "Proton-Driven Amide Bond-Cleavage Pathways of Gas-Phase Peptide Ions Lacking Mobile Protons." *Journal of the American Chemical Society* 131 (39): 14057-14065. https://doi.org/10.1021/ja903883z.

Caboche, Ségolène, Valérie Leclère, Maude Pupin, Gregory Kucherov, and Philippe Jacques. 2010. "Diversity of Monomers in Nonribosomal Peptides: Towards the Prediction of Origin and Biological Activity." *Journal of Bacteriology* 192 (19): 5143-5150. https://doi.org/10.1128/jb.00315-10.

Carr, Steven A., Eric Block, Catherine E. Costello, Ronald F. Vesonder, and H. R. Burmeister. 1985. "Structure Determination of a New Cyclodepsipeptide Antibiotic from Fusaria Fungi." *The Journal of Organic Chemistry* 50 (16): 2854-2858. https://doi.org/10.1021/jo00216a008.

Cavelier, F., C. Enjalbal, J. Martinez, M. Roque, P. Sanchez, and J.-L. Aubagnac. 1999. "Comparison of Collisionally Activated Dissociation Mass Spectra for the Identification of Cyclopeptides and Cyclodepsipeptides." *Rapid Communications in Mass Spectrometry* 13 (10): 880-885. https://doi.org/10.1002/(SICI)1097-0231(19990530)13:10<880::AID-RCM574>3.0.CO;2-1.

Cavelier, Florine, Robert Jacquier, Jean-Luc Mercadier, Jean Verducci, Michel Traris, and Alain Vey. 1997. "Destruxin Analogs: Variations of the α-Hydroxy Acid Side Chain." *The Journal of Peptide Research* 50 (2): 94-101. https://doi.org/10.1111/j.1399-3011.1997.tb01174.x.

Celli, Nicola, Barbara Mariani, Francesco Di Carlo, Massimo Zucchetti, Luis Lopez-Lazaro, Maurizio D'Incalci, and Domenico Rotilio. 2004. "Determination of Aplidin®, a Marine-Derived Anticancer Drug, in Human Plasma, Whole Blood and Urine by Liquid Chromatography with Electrospray Ionisation Tandem Mass Spectrometric Detection." *Journal of Pharmaceutical and Biomedical Analysis* 34 (3): 619-630. https://doi.org/10.1016/S0731-7085(03)00557-0.

Cerda, Blas A., and Chrys Wesdemiotis. 2000. "Zwitterionic vs. Charge-Solvated Structures in the Binding of Arginine to Alkali Metal Ions in the Gas Phase." *Analyst* 125 (4): 657-660. https://doi.org/10.1039/A909220J.

Chan, Wilfred R., Winston F. Tinto, Percy S. Manchand, and Louis J. Todaro. 1987. "Stereostructures of Geodiamolides A and B, Novel Cyclodepsipeptides from the Marine Sponge Geodia Sp." *The Journal of Organic Chemistry* 52 (14): 3091-3093. https://doi.org/10.1021/jo00390a023.

Chen, Qi-Yin, Yanxia Liu, Weijing Cai, and Hendrik Luesch. 2014. "Improved Total Synthesis and Biological Evaluation of Potent Apratoxin S4 Based Anticancer Agents with Differential Stability and Further Enhanced Activity." *Journal of Medicinal Chemistry* 57 (7): 3011-3029. https://doi.org/10.1021/jm4019965.

Chen, Xiaohong, Erin R. Gardner, and William D. Figg. 2008. "Determination of the Cyclic Depsipeptide FK228 in Human and Mouse Plasma by Liquid Chromatography with Mass-Spectrometric Detection." *Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences* 865 (1-2): 153-158. https://doi.org/10.1016/j.jchromb.2008.02.015.

Chen, Yan, Melitta Bilban, Carolyn A. Foster, and Dale L. Boger. 2002. "Solution-Phase Parallel Synthesis of a Pharmacophore Library of HUN-7293 Analogues: A General Chemical Mutagenesis Approach To Defining Structure-Function Properties of Naturally Occurring Cyclic (Depsi)Peptides." *Journal of the American Chemical Society* 124 (19): 5431-5440. https://doi.org/10.1021/ja020166v.

Chow, Hoi Yee, Kathy Hiu Laam Po, Peng Gao, Pilar Blasco, Xiukun Wang, Congran Li, Lianwei Ye, et al. 2020. "Methylation of Daptomycin Leading to the Discovery of Kynomycin, a Cyclic Lipodepsipeptide Active against Resistant Pathogens." *Journal of Medicinal Chemistry* 63 (6): 3161-3171. https://doi.org/10.1021/acs.jmedchem.9b01957.

Ciruela, Francisco, Javier Burgueño, Vicent Casadó, Meritxell Canals, Daniel Marcellino, Steven R. Goldberg, Michael Bader, et al. 2004. "Combining Mass Spectrometry and Pull-Down Techniques for the Study of Receptor Heteromerization. Direct Epitope-Epitope Electrostatic Interactions between Adenosine A2A and Dopamine D2 Receptors." *Analytical Chemistry* 76 (18): 5354-5363. https://doi.org/10.1021/ac049295f.

Clardy, Jon, Michael A. Fischbach, and Christopher T. Walsh. 2006. "New Antibiotics from Bacterial Natural Products." *Nature Biotechnology* 24 (12): 1541-1550. https://doi.org/10.1038/nbt1266.

Clark, Chase M., Maria S. Costa, Laura M. Sanchez, and Brian T. Murphy. 2018. "Coupling MALDI-TOF Mass Spectrometry to the Determination of the α-Hydroxy Acid Side Chain." *Journal of Organic Chemistry* 83 (1): 1101-1108. https://doi.org/10.1021/jo110110g.
Spectrometry Protein and Specialized Metabolite Analyses to Rapidly Discriminate Bacterial Function." Proceedings of the National Academy of Sciences 115 (19): 4981-4986. https://doi.org/10.1073/pnas.1801247115.

Clark, Dale P., Jennifer Carroll, Stephen Naylor, and Phillip Crews. 1998. "An Antifungal Cyclodepsipeptide, Cyclolithistide A, from the Sponge Theonella Swinhoei." The Journal of Organic Chemistry 63 (24): 8757-8764. https://doi.org/10.1021/jo980758p.

Cody, R. B., and B. S. Freiser. 1979. "Electron Impact Excitation of Ions from Organics: An Alternative to Collision Induced Dissociation." Analytical Chemistry 51 (4): 547-551. https://doi.org/10.1021/ac50040a022.

Cole, R. B., S. LeMeillour, and J. C. Tabet. 1992. "Surface-Induced Dissociation of Protonated Peptides: Implications of Initial Kinetic Energy Spread." Analytical Chemistry 64 (4): 365-371. https://doi.org/10.1021/ac00028a009.

Coleman, John E., Rob Van Soest, and Raymond J. Andersen. 1999. "New Geodiamolides from the Sponge Cymbastela Sp. Collected in Papua New Guinea." Journal of Natural Products 62 (8): 1137-1141. https://doi.org/10.1021/np9901550.

Colsch, Benoit, Annelaure Damont, Christophe Junot, François Fenaille, and Jean-Claude Tabet. 2019. "Experimental Evidence That Electrospray-Produced Sodiated Lysophosphatidyl Ester Structures Exist Essentially as Protonated Salts." European Journal of Mass Spectrometry 25 (3): 333-338. https://doi.org/10.1177/1469066719838924.

Colsch, Benoit, François Fenaille, Anna Warnet, Christophe Junot, and Jean-Claude Tabet. 2017. "Mechanisms Governing the Fragmentation of Glycerophospholipids Containing Choline and Ethanolamine Polar Head Groups." European Journal of Mass Spectrometry 23 (6): 427-444. https://doi.org/10.1177/1469066717731668.

Compernolle, F., H. Vanderhaeghe, and G. Janssen. 1972. "Mass Spectra of Staphylomycin S Components and of Related Cyclodepsipeptide Antibiotics." Organic Mass Spectrometry 6 (2): 151-166. https://doi.org/10.1002/oms.1210060205.

Cook, Shannon L., Olivier L. Collin, and Glen P. Jackson. 2009. "Metastable Atom-Activated Dissociation Mass Spectrometry: Leucine/Isoleucine Differentiation and Ring Cleavage of Proline Residues." Journal of Mass Spectrometry 44 (8): 1211-1223. https://doi.org/10.1002/jms.1598.

Cooper, Helen J, Robert R Hudgins, and Alan G Marshall. 2004. "Electron Capture Dissociation Fourier Transform Ion Cyclotron Resonance Mass Spectrometry of Cyclodepsipeptides, Branched Peptides, and ε-Peptides." International Journal of Mass Spectrometry, Special Issue in Honour of Alan G. Marshall, 234 (1): 23-35. https://doi.org/10.1016/j.ijms.2004.01.017.

Cortese, Manuela, Maria Rosa Gigliobianco, Federico Magnoni, Roberta Censi, and Piera Di Martino. 2020. "Compensate for or Minimize Matrix Effects? Strategies for Overcoming Matrix Effects in Liquid Chromatography-Mass Spectrometry Technique: A Tutorial Review." Molecules 25 (13): 3047. https://doi.org/10.3390/molecules25133047.

Crews, Phillip, Lawrence V Manes, and Mark Boehler. 1986. "Jasplakinolide, a Cyclodepsipeptide from the Marine Sponge, Jaspis SP." Tetrahedron Letters 27 (25): 2797-2800. https://doi.org/10.1016/S0040-4039(00)84645-6.

Cruz, Luis J., Andres Francesch, Carmen Cuevas, and Fernando Albericio. 2007. "Synthesis and Structure-Activity Relationship of Cytotoxic Marine Cyclodepsipeptide IB-01212 Analogues." ChemMedChem 2 (7): 1076-1084. https://doi.org/10.1002/cmcc.200700025.

Cruz, Luis J., Marta Martínez Insua, Julia Pérez Baz, Martha Trujillo, Ricard A. Rodriguez-Mias, Eliandre Oliveira, Ernest Giralt, Fernando Albericio, and Librada M. Cañedo. 2006. "IB-01212, a New Cytotoxic Cyclodepsipeptide Isolated from the Marine Fungus Clonostachys Sp. ESNA-A009." The Journal of Organic Chemistry 71 (9): 3335-3338. https://doi.org/10.1021/jo051600p.

Cruz, Luis J., Juan R. Luque-Ortega, Luis Rivas, and Fernando Albericio. 2009. "Kahalalide F, an Antitumor Depsipeptide in Clinical Trials, and Its Analogues as Effective Antileishmanial Agents." Molecular Pharmaceutics 6 (3): 813-824. https://doi.org/10.1021/mp8001039.

Cueto, Mercedes, Paul R Jensen, and William Fenical. 2000. "N-Methylsansalvamide, a Cytotoxic Cyclic Depsipeptide from a Marine Fungus of the Genus Fusarium." Phytochemistry 55 (3): 223-226. https://doi.org/10.1016/S0031-9422(00)00280-6.

Damont, Annelaure, Marie-Françoise Olivier, Anna Warnet, Bernard Lyan, Estelle Pujos-Guillot, Emilien L. Jamin, Laurent Debrauwer, et al. 2019. "Proposal for a Chemically Consistent Way to Annotate Ions Arising from the Analysis of Reference Compounds under ESI Conditions: A Prerequisite to Proper Mass Spectral Database Constitution in Metabolomics." Journal of Mass Spectrometry 54 (6): 567-582. https://doi.org/10.1002/jms.4372.

Daniel, Juliana, Andressa Silva, Danielle Nakagawa, Lívia De Medeiros, Mário Carvalho, Lucineli Tavares, Lucas Abreu, and Edson Rodrigues-Filho. 2017. "Larvicidal Activity of Beauveria Bassiana Extracts against Aedes Aegypti and Identification of Beauvericins." Journal of the Brazilian Chemical Society 28 (6): 1003-1013. https://doi.org/10.21577/0103-5053.20160253.

Darii, Ekaterina, Sandra Alves, Yves Gimbert, Alain Perret, and Jean-Claude Tabet. 2017. "Meaning and Consequence of the Coexistence of Competitive Hydrogen Bond/Salt Forms on the Dissociation Orientation of Non-Covalent Complexes." Journal of Chromatography B, Advances in mass spectrometry-based applications, 1047: 45-58. https://doi.org/10.1016/j.jchromb.2016.09.038.

Darii, Ekaterina, Yves Gimbert, Sandra Alves, Annelaure Damont, Alain Perret, Amina S. Woods, François Fenaille, and Jean-Claude Tabet. 2021. "First Direct Evidence of Interpartner Hydride/Deuteride Exchanges for Stored Sodiated Arginine/Fructose-6-Phosphate Complex Anions within Salt-Solvated Structures." Journal of the American Society for Mass Spectrometry. 32: 1424-1440. https://doi.org/10.1021/jasms.1c00040.

D'Auria, M. Valeria, Luigi Gomez Paloma, Luigi Minale, Angela Zampella, Cécile Debitus, and Joseph Perez. 1995. "Neosiphoniamolide A, a Novel Cyclodepsipeptide, with Antifungal Activity from the Marine Sponge Neosiphonia Superstes." Journal of Natural Products 58 (1): 121-123. https://doi.org/10.1021/np50115a017.

Davies-Coleman, Michael T., Thomas M. Dzeha, Christopher A. Gray, Sonja Hess, Lewis K. Pannell, Denver T. Hendricks, and
Catherine E. Arendse. 2003. "Isolation of Homodolastatin 16, a New Cyclic Depsipeptide from a Kenyan Collection of Lyngbya majuscula." *Journal of Natural Products* 66 (5): 712-715. https://doi.org/10.1021/np030014t.

Debono, Manuel, Bernard J. Abbott, R. Michael Molloy, David S. Fukuda, Ann H. Hunt, Veronica M. Daupert, Frederick T. Counter, et al. 1988. "Enzymatic and Chemical Modifications of Lipopeptide Antibiotic A21978C: The Synthesis and Evaluation of Daptomycin (LY146032)." *The Journal of Antibiotics* 41 (8): 1093-1105. https://doi.org/10.7164/antibiotics.41.1093.

Decleer, Marlies, Sofie Landschoot, Sarah De Saeger, Andrea Rajkovic, and Kris Audenaert. 2019. "Impact of Fungicides and Weather on Cyclodepsipeptide-Producing Fusarium Spp. and Beauvericin and Enniatin Levels in Wheat Grains." *Journal of the Science of Food and Agriculture* 99 (1): 253-262. https://doi.org/10.1002/jsfa.9167.

Decleer, Marlies, Andreja Rajkovic, Benedikt Sas, Annemieke Madder, and Sarah De Saeger. 2016. "Development and Validation of Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry Methods for the Simultaneous Determination of Beauvericin, Enniatins (A, A1, B, B1) and Cereulide in Maize, Wheat, Pasta and Rice." *Journal of Chromatography A* 1472: 35-43. https://doi.org/10.1016/j.chroma.2016.10.003.

Denisov, Eduard, Eugen Damoc, Oliver Lange, and Alexander Makarov. 2012. "Orbitrap Mass Spectrometry with Resolving Powers above 1,000,000." *International Journal of Mass Spectrometry*, Eugene N. Nikolaev 65th Birthday Honor Issue, 325-327:80-85. https://doi.org/10.1016/j.ijms.2012.06.009.

Dierick, Katelijne, Els Van Coillie, Izabela Swiecicka, Geert Meyfroidt, Hugo Devlieger, Agnes Meulemans, Guy Hoedemaekers, Ludo Fourie, Marc Heyndrickx, and Jacques Mahillon. 2005. "Fatal Family Outbreak of Bacillus Cereus-Associated Food Poisoning." *Journal of Clinical Microbiology* 43 (8): 4277-4279. https://doi.org/10.1128/JCM.43.8.4277-4279.2005.

Dirnhofer, R., O. Sonnabend, and W. Sonnabend. 1977. "Eine tödlich verlaufene Lebensmittelvergiftung durch Bacillus cereus." *Zeitschrift für Rechtsmedizin* 80 (2): 139-151. https://doi.org/10.1007/BF01160201.

Doekel, Sascha, Marie-Françoise Coëffet-Le Gal, Jian-Qiao Gu, Min Chu, Richard H. Baltz, and Paul Brian. 2008. "Non-Ribosomal Peptide Synthetase Module Fusions to Produce Derivatives of Daptomycin in Streptomyces Roseosporus." *Microbiology* 154 (9): 2872-2880. https://doi.org/10.1099/mic.0.2008/020685-0.

Du, Feng-Yu, Peng Zhang, Xiao-Ming Li, Chun-Shun Li, Chuan-Ming Cui, and Bin-Gui Wang. 2014. "Cyclohexadepsipeptides of the Isaridin Class from the Marine-Derived Fungus Beauveria Felina EN-135." *Journal of Natural Products* 77 (5): 1164-1169. https://doi.org/10.1021/np4011037.

Du, Yanhua, Yemin Wang, Tingting Huang, Meifeng Tao, Zixin Deng, and Shuangjun Lin. 2014. "Identification and Characterization of the Biosynthetic Gene Cluster of Polyoxypeptin A, a Potent Apoptosis Inducer." *BMC Microbiology* 14 (1): 30. https://doi.org/10.1186/1471-2180-14-30.

Ducrest, P. J., S. Pfammatter, D. Stephan, G. Vogel, P. Thibault, and B. Schnyder. 2019. "Rapid Detection of Bacillus Ionophore

Cereulide in Food Products." *Scientific Reports* 9 (1): 5814. https://doi.org/10.1038/s41598-019-42167-0.

Eckart, Klaus. 1994. "Mass Spectrometry of Cyclic Peptides." *Mass Spectrometry Reviews* 13 (1): 23-55. https://doi.org/10.1002/ mas.1280130104.

Eckart, Klaus, Helmut Schwarz, Kenneth B. Tomer, and Michael L. Gross. 1985. "Tandem Mass Spectrometry Methodology for the Sequence Determination of Cyclic Peptides." *Journal of the American Chemical Society* 107 (24): 6765-6769. https://doi.org/10.1021/ja00310a003.

Edman, Pehr. 1949. "A Method for the Determination of Amino Acid Sequence in Peptides." *Archives of Biochemistry* 22 (3): 475.

Ekman, Jaakko V., Alexey Kruglov, Maria A. Andersson, Raimo Mikkola, Mari Raulio, and Mirja Salkinoja-Salonen. 2012. "Cereulide Produced by Bacillus Cereus Increases the Fitness of the Producer Organism in Low-Potassium Environments." *Microbiology* 158 (4): 1106-1116. https://doi.org/10.1099/mic.0.053520-0.

Feifel, Sven C., Timo Schmiederer, Till Hornbogen, Holger Berg, Roderich D. Süssmuth, and Rainer Zocher. 2007. "In Vitro Synthesis of New Enniatins: Probing the α-D-Hydroxy Carboxylic Acid Binding Pocket of the Multienzyme Enniatin Synthetase." *ChemBioChem* 8 (15): 1767-1770. https://doi.org/10.1002/cbic.200700377.

Feng, Yunjiang, John W. Blunt, Anthony L. J. Cole, and Murray H. G. Munro. 2002. "A Novel Cyclodepsipeptide, HA23, from a Fusarium Sp." *Organic Letters* 4 (12): 2095-2096. https://doi.org/10.1021/ol0260167.

Field, Frank H. 1968. "Chemical Ionization Mass Spectrometry." *Accounts of Chemical Research* 1 (2): 42-49. https://doi.org/10.1021/ar50002a002.

Finking, Robert, and Mohamed A. Marahiel. 2004. "Biosynthesis of Nonribosomal Peptides." *Annual Review of Microbiology* 58 (1): 453-488. https://doi.org/10.1146/annurev.micro.58.030603.123615.

Ford, Paul W., Kirk R. Gustafson, Tawnya C. McKee, Nobuharu Shigematsu, Laura K. Maurizi, Lewis K. Pannell, David E. Williams, et al. 1999. "Papuamides A–D, HIV-Inhibitory and Cytotoxic Depsipeptides from the Sponges Theonella Mirabilis and Theonella Swinhoei Collected in Papua New Guinea." *Journal of the American Chemical Society* 121 (25): 5899-5909. https://doi.org/10.1021/ja990582o.

Fotso, Serge, Paul Graupner, Quanbo Xiong, Jeffrey R. Gilbert, Don Hahn, Cruz Avila-Adame, George Davis, and Kengo Sumiyoshi. 2018. "Alveolarides: Antifungal Peptides from Microascus Alveolaris Active against Phytopathogenic Fungi." *Journal of Natural Products* 81 (1): 10-15. https://doi.org/10.1021/acs.jnatprod.7b00337.

Fournier, I, A Brunot, J. C Tabet, and G Bolbach. 2002. "Delayed Extraction Experiments Using a Repulsive Potential before Ion Extraction: Evidence of Clusters as Ion Precursors in UV-MALDI. Part I: Dynamical Effects with the Matrix 2,5-Dihydroxybenzoic Acid." *International Journal of Mass Spectrometry* 213 (2): 203-215. https://doi.org/10.1016/S1387-3806(01)00540-1.

Fournier, I., A. Brunot, J. C. Tabet, and G. Bolbach. 2005. "Delayed Extraction Experiments Using a Repulsing Potential before Ion Extraction: Evidence of Non-Covalent Clusters as Ion
Precursor in UV Matrix-Assisted Laser Desorption/Ionization. Part II—Dynamic Effects with α-Cyano-4-Hydroxycinnamic Acid Matrix.” *Journal of Mass Spectrometry* 40 (1): 50–59. https://doi.org/10.1002/jms.772.

Fujii, Kiyonaga, Yoshitomo Ikai, Tsuyoshi Mayumi, Hisao Oka, Makoto Suzuki, and Ken-ichi Harada. 1997. "A Nonempirical Method Using LC/MS for Determination of the Absolute Configuration of Constituent Amino Acids in a Peptide: Elucidation of Limitations of Marfey's Method and of Its Separation Mechanism." *Analytical Chemistry* 69 (16): 3346–3352. https://doi.org/10.1021/ac9701795.

Gala, Fulvio, Maria Valeria D'Auria, Simona De Marino, Valentina Sepe, Franco Zollo, Charles D. Smith, Staci N. Keller, and Angela Zampella. 2009. "Jaspamides M-P: New Tryptophan Modified Jaspamide Derivatives from the Sponge Jaspis Splendans." *Tetrahedron* 65 (1): 51–56. https://doi.org/10.1016/j.tet.2008.10.076.

Giltrap, Andrew M., F. P. Jake Haeckl, Kenji L. Kurita, Roger G. Linington, and Richard J. Payne. 2018. "Synthetic Studies Toward the Skyllamycins: Total Synthesis and Generation of Simplified Analogues." *The Journal of Organic Chemistry* 83 (13): 7250–7270. https://doi.org/10.1021/acs.joc.8b00898.

Glasset, Benjamin, Sabine Herbin, Laurent Guillier, Sabrina Cadel-Six, Marie-Léone Vignaud, Joel Grout, Sylvie Pairaud, et al. 2016. "Bacillus Cereus-Induced Food-Borne Outbreaks in France, 2007 to 2014: Epidemiology and Genetic Characterisation." *Eurosurveillance* 21 (48): 30413. https://doi.org/10.2807/1560-7917.ES.2016.21.48.30413.

Gomes, Aldrin V. 2022. "On 'A Method for the Determination of Amino Acid Sequence in Peptides' by P. Edman." *Archives of Biochemistry and Biophysics* 726: 109304. https://doi.org/10.1016/j.abb.2022.109304.

González-Jartín, Jesús M., Inés Rodríguez-Cañás, Amparo Alfonso, María J. Sainz, Mercedes R. Vieytes, Ana Gomes, Isabel Ramos, and Luis M. Botana. 2021. "Multianalyte Method for the Determination of Regulated, Emerging and Modified Mycotoxins in Milk: QuECHERS Extraction Followed by UHPLC-MS/MS Analysis." *Food Chemistry* 356: 129647. https://doi.org/10.1016/j.foodchem.2021.129647.

Gord, James R., Stevan R. Horning, Joseph M. Wood, R. Graham Cooks, and Ben S. Freiser. 1993. "Energy Deposition during Electron-Induced Dissociation." *Journal of the American Society for Mass Spectrometry* 4 (2): 145–151. https://doi.org/10.1016/1044-0305(93)85070-E.

Grünewald, Jan, and Mohamed A. Marahiel. 2006. "Chemoenzymatic and Template-Directed Synthesis of Bioactive Macrocyclic Peptides." *Microbiology and Molecular Biology Reviews* 70 (1): 121–146. https://doi.org/10.1128/mmbr.70.1.121-146.2006.

Guenzi, Eric, Giuliano Galli, Ingeborg Grgurina, Dennis C. Gross, and Guido Grandi. 1998. "Characterization of the Syr-ingomycin Synthetase Gene Cluster: A Link Between Pro-karyotic and Eukaryotic Peptide Synthetases*." *Journal of Biological Chemistry* 273 (49): 32857–32863. https://doi.org/10.1074/jbc.273.49.32857.

Häggblom, Max M, Camelia Apetroaie, Maria A. Andersson, and Mirja S. Salkinoja-Salonen. 2002. "Quantitative Analysis of Cereulide, the Emetic Toxin of Bacillus Cereus, Produced under Various Conditions." *Applied and Environmental Microbiology* 68 (5): 2479–2483. https://doi.org/10.1128/AEM.68.5.2479-2483.2002.

Hale, Karl J., and Linos Lazarides. 2002. "Synthetic Route to the GE3 Cyclodepsipeptide." *Organic Letters* 4 (11): 1903–1906. https://doi.org/10.1021/ol025895u.

Hall, M. J. 1970. "Mode of Action of Monamycin. Evidence for the Formation of a Complex between the Monamycin Cyclo-depsipeptide Antibiotics and Some Cations in Solution." *Biochemical and Biophysical Research Communications* 38 (4): 590–598. https://doi.org/10.1016/0006-291X(70)90622-4.

Han, Bingnan, Doug Goeger, Claudia S. Maier, and William H. Gerwick. 2005. "The Wewakpeptins, Cyclic Depsipeptides from a Papua New Guinea Collection of the Marine Cyanobacterium Lyngbya semiplena." *The Journal of Organic Chemistry* 70 (8): 3133–3139. https://doi.org/10.1021/jo0478858.

Hart, Kevin J., Scott A. McLuckey, and Gary L. Glish. 1992. "Evidence of Isomerization during Ion Isolation in the Quadrupole Ion Trap." *Journal of the American Society for Mass Spectrometry* 3 (6): 680–682. https://doi.org/10.1016/1044-0305(92)85010-H.

He, Wei, Hai-Bo Qiu, Yi-Jie Chen, Jie Xi, and Zhu-Jun Yao. 2014. "Total Synthesis of Proposed Structure of Coibamide A, a Highly N- and O-Methylated Cytotoxic Marine Cyclodepsipeptide." *Tetrahedron Letters* 55 (44): 6109–6112. https://doi.org/10.1016/j.tetlet.2014.09.047.

Hegge, Anne, Rikke Lønborg, Ditte Møller Nielsen, and Jens Laurids Sørensen. 2015. "Factors Influencing Production of Fusaristatin A in Fusarium Graminearum." *Metabolites* 5 (2): 184–191. https://doi.org/10.3390/metabo5020184.

Herath, Kithsiri, Guy Harris, Hiranthi Jayasuriya, Deborah Zink, Scott Smith, Francisca Vicente, Gerald Bills, et al. 2009. "Isolation, Structure and Biological Activity of Phomafungin, a Cyclic Lipodepsipeptide from a Widespread Tropical Phoma Sp." *Bioorganic & Medicinal Chemistry, Tetrahedron Young Investigator Award 2006: Jonathan Ellman*, 17 (3): 1361–1369. https://doi.org/10.1016/j.bmc.2008.12.009.

Hojati, Zohreh, Claire Milne, Barbara Harvey, Lyndsey Gordon, Matthew Borg, Fiona Flett, Barrie Wilkinson, et al. 2002. "Structure, Biosynthetic Origin, and Engineered Biosynthesis of Calcium-Dependent Antibiotics from Streptomyces Coelicolor." *Chemistry & Biology* 9 (11): 1175–1187. https://doi.org/10.1016/S1074-5521(02)00252-1.

Horng, Yi-Bing, Yu-Hsiang Yu, Andrzej Dybus, Felix Shih-Hsiang Hsiao, and Yeong-Hsiang Cheng. 2019. "Antibacterial Activity of Bacillus Species-Derived Surfactin on Brachyspira Hyodysenteriae and Clostridium Perfringens." *AMB Express* 9 (1): 188. https://doi.org/10.1186/s13568-019-0914-2.

Huang, Shuhui, Yushi Liu, Wan-Qiu Liu, Peter Neubauer, and Jian Li. 2021. "The Nonribosomal Peptide Valinomycin: From Discovery to Bioactivity and Biosynthesis." *Microorganisms* 9 (4): 780. https://doi.org/10.3390/microorganisms9040780.

Hwang, Ji-Yeon, Jung-Ho Lee, Sung Chul Park, Jayho Lee, Dong-Chan Oh, Ki-Bong Oh, and Jongheon Shin. 2019. "New Peptides from The Marine-Derived Fungi Aspergillus Allahabadii and Aspergillus Ochraceopetaliformis." *Marine Drugs* 17 (9): 488. https://doi.org/10.3390/md17090488.

Iizuka, Takashi, Ryosuke Fudou, Yasuko Jojima, Sumie Ogawa, Shigeru Yamanaka, Yasutaka Inukai, and Makoto Ojika. 2006.
"Miuraenamides A and B, Novel Antimicrobial Cyclic Depsipeptides from a New Slightly Halophilic Myxobacterium: Taxonomy, Production, and Biological Properties." *The Journal of Antibiotics* 59 (7): 385-391. https://doi.org/10.1038/ja.2006.55.

International Union of Pure and Applied Chemistry (IUPAC). 2006. "Depsipeptides." https://doi.org/10.1351/goldbook.D01604.

Isaka, Masahiko, Pitchapa Berkaew, Kamolphan Intereya, Somjit Komwijjit, and Thiptiwa Sathitkunanon. 2007. "Antiplasmodial and Antiviral Cyclohexadepsipeptides from the Endophytic Fungus Pullularia Sp. BCC 8613." *Tetrahedron* 63 (29): 6855-6860. https://doi.org/10.1016/j.tet.2007.04.062.

Isaka, Masahiko, Somporn Palasarn, Sanisa Lapanun, and Kanlayanee Sriklung. 2007. "Paecilodepsipeptide A, an Antimalarial and Antitumor Cyclohexadepsipeptide from the Insect Pathogenic Fungus Paecilomyces Cinnamomeus BCC 9616." *Journal of Natural Products* 70 (4): 675-678. https://doi.org/10.1021/np060602h.

Isaka, Masahiko, Somporn Palasarn, Kanlayanee Sriklung, and Kanokarn Kocharin. 2005. "Cyclohexadepsipeptides from the Insect Pathogenic Fungus Hirsutella Nivea BCC 2594." *Journal of Natural Products* 68 (11): 1680-1682. https://doi.org/10.1021/np050246n.

Ishiyama, Daisuke, Tsutomu Sato, Reiko Honda, Hisato Senda, Hiroshi Konno, and Susumu Kanazawa. 2000. "Glomosporin, a Novel Antifungal Cyclic Depsipeptide from Glomospora Sp. II. Structure Elucidation." *The Journal of Antibiotics* 53 (5): 525-531. https://doi.org/10.7164/antibiotics.53.525.

Jääskeläinen, Elina L., Max M. Häggblom, Maria A. Andersson, Liisa Vanne, and Mirja S. Salkinoja-Salonen. 2003. "Potential of Bacillus Cereus for Producing an Emetic Toxin, Cereulide, in Bakery Products: Quantitative Analysis by Chemical and Biological Methods." *Journal of Food Protection* 66 (6): 1047-1054. https://doi.org/10.4315/0362-028X-66.6.1047.

Jackson, Shelley N., Hay-Yan J. Wang, Alfred Yergey, and Amina S. Woods. 2006. "Phosphate Stabilization of Intermolecular Interactions." *Journal of Proteome Research* 5 (1): 122-126. https://doi.org/10.1021/pr0503578.

Jaitzig, Jennifer, Jian Li, Roderich D. Süssmuth, and Peter Neubauer. 2014. "Reconstituted Biosynthesis of the Non-ribosomal Macrolactone Antibiotic Valinomycin in Escherichia coli." ACS Synthetic Biology 3 (7): 432-438. https://doi.org/10.1021/sb400082j.

Jardine, Ian, and Catherine Fenselau. 1976. "Proton Localization in Chemical Ionization Fragmentation." *Journal of the American Chemical Society* 98 (17): 5086-5089. https://doi.org/10.1021/ja00433a006.

Jegorov, Alexandr, Marian Hajduch, Miroslav Sulc, and Vladimir Havlicek. 2006. "Nonribosomal Cyclic Peptides: Specific Markers of Fungal Infections." *Journal of Mass Spectrometry: JMS* 41 (5): 563-576. https://doi.org/10.1002/jms.1042.

Jegorov, Alexandr, Vladimír Havlíček, and Petr Sedmera. 1998. "Rapid Screening of Destruxins by Liquid Chromatography/ Mass Spectrometry." *Journal of Mass Spectrometry* 33 (3): 274-280. https://doi.org/10.1002/(SICI)1096-9888(199803)33:3<274::AID-JMS630>3.0.CO;2-R.

Jegorov, Alexandr, Bela Paizs, Marek Kuzma, Martin Zabka, Zdeněk Landa, Miroslav Sulc, Mark P. Barrow, and Vladimir

Havlicek. 2004. "Extraribosomal Cyclic Tetradepsipeptides Beauverolides: Profiling and Modeling the Fragmentation Pathways." *Journal of Mass Spectrometry* 39 (8): 949-960. https://doi.org/10.1002/jms.674.

Jegorov, Alexandr, Petr Sedmera, Vladimír Maťha, Petr Šimek, Helena Zahradníčková, Zdeněk Landa, and Jacob Eyal. 1994. "Beauverolides L and La from Beauveria Tenella and Paecilomyces Fumosoroseus." *Phytochemistry, The International Journal of Plant Biochemistry*, 37 (5): 1301-1303. https://doi.org/10.1016/S0031-9422(00)90402-3.

Jenkins, Kelly M., Matthew K. Renner, Paul R. Jensen, and William Fenical. 1998. "Exumolides A and B: Antimicroalgal Cyclic Depsipeptides Produced by a Marine Fungus of the Genus Scytalidium." *Tetrahedron Letters* 39 (17): 2463-2466. https://doi.org/10.1016/S0040-4039(98)00288-3.

Jiang, Wei, Panpan Ye, Chen-Tung Arthur Chen, Kuiwu Wang, Pengyuan Liu, Shan He, Xiaodan Wu, Lishe Gan, Ying Ye, and Bin Wu. 2013. "Two Novel Hepatocellular Carcinoma Cycle Inhibitory Cyclodepsipeptides from a Hydrothermal Vent Crab-Associated Fungus Aspergillus Clavatus C2WU." *Marine Drugs* 11 (12): 4761-4772. https://doi.org/10.3390/ md11124761.

Julian, Ryan R., J. L. Beauchamp, and William A. Goddard. 2002. "Cooperative Salt Bridge Stabilization of Gas-Phase Zwitterions in Neutral Arginine Clusters." *The Journal of Physical Chemistry A* 106 (1): 32-34. https://doi.org/10.1021/jp013205i.

Kaida, Kenichi, Yoshihiro Suzukid, Makoto Ojikad, and Youji SakagamId. 2001. "New Cyclic Depsipeptide Antibiotics, Clavariopsins A and B, Produced by an Aquatic Hyphomycetes, Clavariopsis Aquatica 1. Taxonomy, Fermentation, Isolation, and Biological Properties." *The Journal of Antibiotics*; 54; 17-21.

Kailasa, Suresh Kumar, and Hui-Fen Wu. 2010. "Surface Modified Silver Selinide Nanoparticles as Extracting Probes to Improve Peptide/Protein Detection via Nanoparticles-Based Liquid Phase Microextraction Coupled with MALDI Mass Spectrometry." *Talanta* 83 (2): 527-534. https://doi.org/10.1016/j. talanta.2010.09.040.

Kajimura, Yoshio, and Miyuki Kaneda. 1996. "Fusaricidin A, a New Depsipeptide Antibiotic Produced by Bacillus Polymyxa KT-8 Taxonomy, Fermentation, Isolation, Structure Elucidation and Biological Activity." *The Journal of Antibiotics* 49 (2): 129-135. https://doi.org/10.7164/antibiotics.49.129.

Kang, Hee Kyoung, Moon-Chang Choi, Chang Ho Seo, and Yoonkyung Park. 2018. "Therapeutic Properties and Biological Benefits of Marine-Derived Anticancer Peptides." *International Journal of Molecular Sciences* 19 (3): 919. https:// doi.org/10.3390/ijms19030919.

Kang, Sangwook, Jaeho Han, Sung Chul Jang, Joon Soo An, Ilnam Kang, Yun Kwon, Sang-Jip Nam, et al. 2022. "Epoxinnamide: An Epoxy Cinnamoyl-Containing Nonribosomal Peptide from an Intertidal Mudflat-Derived Streptomyces Sp." *Marine Drugs* 20 (7): 455. https://doi.org/10.3390/ md20070455.

Karas, Michael., Doris. Bachmann, and Franz. Hillenkamp. 1985. "Influence of the Wavelength in High-Irradiance Ultraviolet Laser Desorption Mass Spectrometry of Organic Molecules." *Analytical Chemistry* 57 (14): 2935-2939. https://doi.org/10. 1021/ac00291a042.
Karas, Michael, Matthias Glückmann, and Jürgen Schäfer. 2000. “Ionization in Matrix-Assisted Laser Desorption/Ionization: Singly Charged Molecular Ions Are the Lucky Survivors.” *Journal of Mass Spectrometry* 35 (1): 1–12. https://doi.org/10.1002/(SICI)1096-9888(200001)35:1<1::AID-JMS904>3.0.CO;2-0.

Kebarle, Paul, and Udo H. Verkerk. 2009. “Electrospray: From Ions in Solution to Ions in the Gas Phase, What We Know Now.” *Mass Spectrometry Reviews* 28 (6): 898–917. https://doi.org/10.1002/mas.20247.

Keller, Lena, Kirley Marques Canuto, Chenxi Liu, Brian M. Suzuki, Jehad Almaliti, Asfandyar Sikandar, C. Benjamin Naman, et al. 2020. “Tutuilamides A–C: Vinyl-Chloride-Containing Cyclodepsipeptides from Marine Cyanobacteria with Potent Elastase Inhibitory Properties.” *ACS Chemical Biology* 15 (3): 751–757. https://doi.org/10.1021/acscchembio.9b00992.

Khosla, Chaitan, Rajesh S. Gokhale, John R. Jacobsen, and David E. Cane. 1999. “Tolerance and Specificity of Polyketide Synthases.” *Annual Review of Biochemistry* 68 (1): 219–253. https://doi.org/10.1146/annurev.biochem.68.1.219.

Kim, Min-Young, Jae Hak Sohn, Jong Seog Ahn, and Hyuncheol Oh. 2009. “Alternaramide, a Cyclic Depsipeptide from the Marine-Derived Fungus Alternaria Sp. SF-5016.” *Journal of Natural Products* 72 (11): 2065–2068. https://doi.org/10.1021/np900464p.

Kirk, Riley D., Haiyin He, Paul G. Wahome, ShiBiao Wu, Guy T. Carter, and Matthew J. Bertin. 2021. “New Micropeptins with Anti-Neuroinflammatory Activity Isolated from a Cyanobacterial Bloom.” *ACS Omega* 6 (23): 15472–15478. https://doi.org/10.1021/acsomega.1c02025.

Kirschning, Andreas, and Frank Hahn. 2012. “Merging Chemical Synthesis and Biosynthesis: A New Chapter in the Total Synthesis of Natural Products and Natural Product Libraries.” *Angewandte Chemie International Edition* 51 (17): 4012–4022. https://doi.org/10.1002/anie.201107386.

Kiryushkin, A. A., V. M. Burikov, and B. V. Rosinov. 1967. “Mass Spectrometric Study of Cyclodepsipeptides. Staphylomycin S.” *Tetrahedron Letters* 8 (28): 2675–2678. https://doi.org/10.1016/S0040-4039(01)89973-1.

Kishimoto, Shinji, Yuta Tsunematsu, Shinichi Nishimura, Yutaka Hayashi, Akira Hattori, and Hideaki Kakeya. 2012. “Tumescenamide C, an Antimicrobial Cyclic Lipodepsipeptide from Streptomyces Sp.” *Tetrahedron* 68 (27): 5572–5578. https://doi.org/10.1016/j.tet.2012.04.075.

Koike, Hiroshi, Maki Kanda, Chie Monma, Souichi Yoshikawa, Hiroshi Hayashi, Yoko Matsushima, Yumi Ohba, et al. 2024. “Development of a Simple Screening Method for Analyzing Cereulide Toxin in Fried Rice Using Liquid Chromatography-Tandem Mass Spectrometry.” *Forensic Toxicology*, 42: 163–171. https://doi.org/10.1007/s11419-024-00683-3.

Krause, Martin, Antje Lindemann, Mirko Gnnski, Till Hornbogen, Gerhard Bonse, Peter Jeschke, Gerhard Tmelking, Wolfgang Gau, Horst Kleinkauf, and Rainer Zocher. 2001. “Directed Biosynthesis of New Enniatins.” *The Journal of Antibiotics* 54 (10): 797–804. https://doi.org/10.7164/antibiotics.54.797.

Kwan, Jason C., Ranjala Ratnayake, Khalil A. Abboud, Valerie J. Paul, and Hendrik Luesch. 2010. “Grassypeptolides A–C, Cytotoxic Bis-Thiazoline Containing Marine Cyclodepsipeptides.” *The Journal of Organic Chemistry* 75 (23): 8012–8023. https://doi.org/10.1021/jo1013564.

Kwan, Jason C., James R. Rocca, Khalil A. Abboud, Valerie J. Paul, and Hendrik Luesch. 2008. “Total Structure Determination of Grassypeptolide, a New Marine Cyanobacterial Cytotoxin.” *Organic Letters* 10 (5): 789–792. https://doi.org/10.1021/ol702946d.

Lam, Kin Sing, Grace A. Hesler, Jacqueline M. Mattei, Stephen W. Mamber, Salvatore Forenza, and Koji Tomita. 1990. “Himastatin, a New Antitumor Antibiotic from Streptomyces Hygroscopicus. I. Taxonomy of Producing Organism, Fermentation and Biological Activity.” *The Journal of Antibiotics* 43 (8): 956–960. https://doi.org/10.7164/antibiotics.43.956.

Lang, Gerhard, Tim Kalvelage, Arne Peters, Jutta Wiese, and Johannes F. Imhoff. 2008. “Linear and Cyclic Peptides from the Entomopathogenic Bacterium Xenorhabdus Nematophilus.” *Journal of Natural Products* 71 (6): 1074–1077. https://doi.org/10.1021/np800053n.

Lange, C., C. Loutelier, and R. S. Bordoli. 1994. “Sequential Product-Ion Spectra (MS3) with Array Detection and Reaction-Intermediate Scanning of a Cyclopeptide on a Five-Sector Mass Spectrometer.” *Rapid Communications in Mass Spectrometry* 8 (12): 960–966. https://doi.org/10.1002/rcm.1290081211.

Lange, C., C. Mulheim, A. Vey, M. Pais, and J.-L. Aubagnac. 1991. “Direct Determination of the Sequence of Destroxins (Cyclodepsipeptides) Using Negative-Ion Fast-Atom Bombardment Mass Spectrometry.” *Rapid Communications in Mass Spectrometry* 5 (2): 86–91. https://doi.org/10.1002/rcm.1290050209.

Langenfeld, Aude, Alain Blond, Sabelle Gueye, Patrick Herson, Bastien Nay, Joëlle Dupont, and Soizic Prado. 2011. “Insecticidal Cyclodepsipeptides from Beauveria Felina.” *Journal of Natural Products* 74 (4): 825–830. https://doi.org/10.1021/np100890n.

Le, Tu Cam, Sultan Pulat, Jihye Lee, Geum Jin Kim, Haerin Kim, Eun-Young Lee, Prima F. Hillman, et al. 2022. “Marine Depsipeptide Nobilamide I Inhibits Cancer Cell Motility and Tumorigenicity via Suppressing Epithelial–Mesenchymal Transition and MMP2/9 Expression.” *ACS Omega* 7 (2): 1722–1732. https://doi.org/10.1021/acsomega.1c04520.

Lee, Hee-Seok, and Chan Lee. 2012. “Structural Analysis of a New Cytotoxic Demethylated Analogue of Neo-N-Methylsansalvamide with a Different Peptide Sequence Produced by Fusarium Solani Isolated from Potato.” *Journal of Agricultural and Food Chemistry* 60 (17): 4342–4347. https://doi.org/10.1021/jf205217v.

Lee, Kit K., James B. Gloer, James A. Scott, and David Malloch. 1995. “Petriellin A: A Novel Antifungal Depsipeptide from the Coprophilous Fungus Petriella Sordida.” *The Journal of Organic Chemistry* 60 (17): 5384–5385. https://doi.org/10.1021/jo00122a010.

Levert, Annabel, Rebeca Alvariño, Louis Bornancin, Eliane Abou Mansour, Adam M. Burja, Anne-Marie Genevière, Isabelle Bonnard, Eva Alonso, Luis Botana, and Bernard Banaigs. 2018. “Structures and Activities of Tiahuramides A–C, Cyclic Depsipeptides from a Tahitian Collection of the Marine Cyanobacterium Lyngbya Majuscula.” *Journal of Natural Products* 75 (23): 8012–8023. https://doi.org/10.1021/jo1013564.
81 (6): 1301-1310. https://doi.org/10.1021/acs.jnatprod.7b00751.

Levsen, Karsten. 1978. *Fundamental Aspects of Organic Mass Spectrometry*. 1. Aufl. Weinheim; Verlag Chemie.

Li, Jesse W.-H., and John C. Vederas. 2009. "Drug Discovery and Natural Products: End of an Era or an Endless Frontier?" *Science* 325 (5937): 161–165. https://doi.org/10.1126/science.1168243.

Li, Yihong, Ning He, Mengna Luo, Bin Hong, and Yunying Xie. 2020. "Application of Untargeted Tandem Mass Spectrometry with Molecular Networking for Detection of Enniatins and Beauvericins from Complex Samples." *Journal of Chromatography A* 1634: 461626. https://doi.org/10.1016/j.chroma.2020.461626.

Li, Yueying, Hao-Bing Yu, Yi Zhang, Tiago Leao, Evgenia Glukhov, Marsha L. Pierce, Chen Zhang, et al. 2020. "Pagoamide A, a Cyclic Depsipeptide Isolated from a Cultured Marine Chlorophyte, Derbesia Sp., Using MS/MS-Based Molecular Networking." *Journal of Natural Products* 83 (3): 617–625. https://doi.org/10.1021/acs.jnatprod.9b01019.

Liao, Jingyuan, Xuelei Jia, Fusong Wu, Junrong Huang, Guifu Shen, Hengzhi You, and Fen-Er Chen. 2022. "Rapid Mild Macrocyclization of Depsipeptides under Continuous Flow: Total Syntheses of Five Cyclodepsipeptides." *Organic Chemistry Frontiers* 9 (23): 6640–6645. https://doi.org/10.1039/D2QO01577C.

Linington, Roger G., Daniel J. Edwards, Cynthia F. Shuman, Kerry L. McPhail, Teatulohi Matalainaho, and William H. Gerwick. 2008. "Symplocamide A, a Potent Cytotoxin and Chymotrypsin Inhibitor from the Marine Cyanobacterium Symploca Sp." *Journal of Natural Products* 71 (1): 22–27. https://doi.org/10.1021/np070280x.

Little, Daniel P., J. Paul. Speir, Michael W. Senko, Peter B. O'Connor, and Fred W. McLafferty. 1994. "Infrared Multi-photon Dissociation of Large Multiply Charged Ions for Biomolecule Sequencing." *Analytical Chemistry* 66 (18): 2809–2815. https://doi.org/10.1021/ac00090a004.

Liu, Si-Xuan, Si-Yi Ou-Yang, Yong-Fu Lu, Chun-Lin Guo, Si-Yang Dai, Chang Li, Tian-Yi Yu, and Yue-Hu Pei. 2023. "Recent Advances on Cyclodepsipeptides: Biologically Active Compounds for Drug Research." *Frontiers in Microbiology* 14: 1276928. https://www.frontiersin.org/articles/10.3389/fmicb.2023.1276928.

Liu, Wei-Ting, Julio Ng, Dario Meluzzi, Nuno Bandeira, Marcelino Gutierrez, Thomas L. Simmons, Andrew W. Schultz, et al. 2009. "Interpretation of Tandem Mass Spectra Obtained from Cyclic Nonribosomal Peptides." *Analytical Chemistry* 81 (11): 4200–4209. https://doi.org/10.1021/ac900114t.

Liuu, Sophie, Kam eng Trinh, Ekaterina Darii, Chenqin Cao, Annelaure Damont, Yves Gimbert, François Fenaille, et al. 2024. "Charge-Solvated versus Protonated Salt Forms of Cyclodepsipeptide Toxins in Electrospray: Dissociation of Alkali-Cationized Forms Enables Straightforward Sequencing of Cereulide." *Journal of Mass Spectrometry* 59 (6): e5037. https://doi.org/10.1002/jms.5037.

Liuzzi, Vania C., Valentina Mirabelli, Maria Teresa Cimmarusti, Miriam Haidukowski, John F. Leslie, Antonio F. Logrieco, Rocco Caliandro, Francesca Fanelli, and Giuseppina

Mulè. 2017. "Enniatin and Beauvericin Biosynthesis in Fusarium Species: Production Profiles and Structural Determinant Prediction." *Toxins* 9 (2): 45. https://doi.org/10.3390/toxins9020045.

Loutelier, C., M. Hubert, A. Marcual, C. Lange, J-L. Mercadier, F. Cavelier, J. Verducci, and R. Jacquier. 1995. "Gas-Phase Reactivity of Protonated Cyclodepsipeptidic Toxins: The Study of a Systematic Fragmentation Pathway under Fast-Atom Bombardment Desorption." *Rapid Communications in Mass Spectrometry* 9 (15): 1512-1515. https://doi.org/10.1002/rcm.1290091510.

Loutelier, C., A. Marcual, J.-C. Cherton, and C. Lange. 1994. "Characterization of Cyclodepsipeptide-Glutathionyl Conjugates by Negative-Ion Fast-Atom Bombardment Linked-Scan Mass Spectrometry." *Rapid Communications in Mass Spectrometry* 8 (12): 957-959. https://doi.org/10.1002/rcm.1290081210.

Lu, Zhenyu, Ryan M. Van Wagoner, Mary Kay Harper, Heather L. Baker, John N. A. Hooper, Carole A. Bewley, and Chris M. Ireland. 2011. "Mirabamides E-H, HIV-Inhibitory Depsipeptides from the Sponge Stelletta Clavosa." *Journal of Natural Products* 74 (2): 185-193. https://doi.org/10.1021/np100613p.

Luesch, Hendrik, Wesley Y. Yoshida, Richard E. Moore, Valerie J. Paul, and Thomas H. Corbett. 2001. "Total Structure Determination of Apratoxin A, a Potent Novel Cytotoxin from the Marine Cyanobacterium Lyngbya m Azuscula." *Journal of the American Chemical Society* 123 (23): 5418-5423. https://doi.org/10.1021/ja010453j.

Mabud, Md.A., Michael J. Dekrey, and R. Graham Cooks. 1985. "Surface-Induced Dissociation of Molecular Ions." *International Journal of Mass Spectrometry and Ion Processes* 67 (3): 285-294. https://doi.org/10.1016/0168-1176(85)83024-X.

Macdonald, C. G., and J. S. Shannon. 1964. "The Structure of the Cyclodepsipeptide, Angolide." *Tetrahedron Letters* 5 (42): 3113-3118. https://doi.org/10.1016/S0040-4039(01)89431-4.

Macdonald, C. G., J. S. Shannon, and A. Taylor. 1964. "Mass Spectra of Cyclic Depsipeptides: Sporidesmolides." *Tetrahedron Letters* 5 (31): 2087-2092. https://doi.org/10.1016/S0040-4039(01)89459-4.

Macias, Luis A., Inês C. Santos, and Jennifer S. Brodbelt. 2020. "Ion Activation Methods for Peptides and Proteins." *Analytical Chemistry* 92 (1): 227-251. https://doi.org/10.1021/acs. analchem.9b04859.

Maharani, Rani, Robert T.C. Brownlee, Andrew B. Hughes, and Belinda M. Abbott. 2014. "A Total Synthesis of a Highly N-Methylated Cyclodepsipeptide [2S,3S-Hmp]-Aureobasidin L Using Solid-Phase Methods." *Tetrahedron* 70 (14): 2351-2358. https://doi.org/10.1016/j.tet.2014.02.036.

Mahler Hellmut, Pasi Aurelio, Kramer John M., Schulte Petra, Scoging Anne C., Bär Walter, and Krähenbühl Stephan. 1997. "Fulminant Liver Failure in Association with the Emetic Toxin of Bacillus Cereus." *New England Journal of Medicine* 336 (16): 1142-1148. https://doi.org/10.1056/NEJM199704173361604.

Makarov, Alexander. 2000. "Electrostatic Axially Harmonic Orbital Trapping: A High-Performance Technique of Mass Analysis." *Analytical Chemistry* 72 (6): 1156-1162. https://doi.org/10.1021/ac991131p.
Marshall, Alan G., Christopher L. Hendrickson, and George S. Jackson. 1998. "Fourier Transform Ion Cyclotron Resonance Mass Spectrometry: A Primer." *Mass Spectrometry Reviews* 17 (1): 1–35. https://doi.org/10.1002/(SICI)1098-2787(1998)17:1<1::AID-MAS1>3.0.CO;2-K.

Martín, María Jesús, Raquel Rodríguez-Acebes, Yésica García-Ramos, Valentín Martínez, Carmen Murcia, Isabel Digón, Isabel Marco, et al. 2014. "Stellatolides, a New Cyclodepsipeptide Family from the Sponge Ecionemia Acervus: Isolation, Solid-Phase Total Synthesis, and Full Structural Assignment of Stellatolide A." *Journal of the American Chemical Society* 136 (18): 6754–6762. https://doi.org/10.1021/ja502744a.

Maruyama, Chitose, Yukiko Chinone, Shusuke Sato, Fumitaka Kudo, Kosuke Ohsawa, Junya Kubota, Junko Hashimoto, et al. 2020. "C-Methylation of S-Adenosyl-L-Methionine Occurs Prior to Cyclopropanation in the Biosynthesis of 1-Amino-2-Methylcyclopropanecarboxylic Acid (Norcoronamic Acid) in a Bacterium." *Biomolecules* 10 (5): 775. https://doi.org/10.3390/biom10050775.

Marxen, Sandra, Timo D. Stark, Elrike Frenzel, Andrea Rütschle, Genia Lücking, Gabriel Pürstinger, Elena E. Pohl, Siegfried Scherer, Monika Ehling-Schulz, and Thomas Hofmann. 2015. "Chemodiversity of Cereulide, the Emetic Toxin of Bacillus Cereus." *Analytical and Bioanalytical Chemistry* 407 (9): 2439–2453. https://doi.org/10.1007/s00216-015-8511-y.

Marxen, Sandra, Timo D. Stark, Andrea Rütschle, Genia Lücking, Elrike Frenzel, Siegfried Scherer, Monika Ehling-Schulz, and Thomas Hofmann. 2015. "Multiparametric Quantitation of the Bacillus Cereus Toxins Cereulide and Isocereulides A–G in Foods." *Journal of Agricultural and Food Chemistry* 63 (37): 8307–8313. https://doi.org/10.1021/acs.jafc.5b03705.

Matsuyama, T, K Kaneda, Y Nakagawa, K Isa, H Hara-Hotta, and I Yano. 1992. "A Novel Extracellular Cyclic Lipopeptide Which Promotes Flagellum-Dependent and -Independent Spreading Growth of Serratia Marcescens." *Journal of Bacteriology* 174 (6): 1769–1776. https://doi.org/10.1128/jb.174.6.1769-1776.1992.

Matter, Andrea M., Sara B. Hoot, Patrick D. Anderson, Susana S. Neves, and Yi-Qiang Cheng. 2009. "Valinomycin Biosynthetic Gene Cluster in Streptomyces: Conservation, Ecology and Evolution." *PLoS ONE* 4 (9): e7194. https://doi.org/10.1371/journal.pone.0007194.

Matthes, Diana, Lennart Richter, Jane Müller, Alexander Denisiuk, Sven C. Feifel, Yuquan Xu, Patricia Espinosa-Artiles, Roderich D. Süssmuth, and István Molnár. 2012. "In Vitro Chemoenzymatic and in Vivo Biocatalytic Syntheses of New Beauvericin Analogues." *Chemical Communications* 48 (45): 5674–5676. https://doi.org/10.1039/C2CC31669B.

Matthew, Susan, Valerie J. Paul, and Hendrik Luesch. 2009. "Tiglicamides A–C, Cyclodepsipeptides from the Marine Cyanobacterium Lyngbya confervoides." *Phytochemistry* 70 (17–18): 2058–2063. https://doi.org/10.1016/j.phytochem.2009.09.010.

Matthew, Susan, Ranjala Ratnayake, Mikel A. Becerro, Raphael Ritson-Williams, Valerie J. Paul, and Hendrik Luesch. 2010. "Intramolecular Modulation of Serine Protease Inhibitor Activity in a Marine Cyanobacterium with Antifeedant Properties." *Marine Drugs* 8 (6): 1803–1816. https://doi.org/10.3390/md8061803.

Matthew, Susan, Lilibeth A. Salvador, Peter J. Schupp, Valerie J. Paul, and Hendrik Luesch. 2010. "Cytotoxic Halogenated

Macrolides and Modified Peptides from the Apratoxin-Producing Marine Cyanobacterium Lyngbya Bouillonii from Guam." *Journal of Natural Products* 73 (9): 1544–1552. https://doi.org/10.1021/np1004032.

Mevers, Emily, Wei-Ting Liu, Niclas Engene, Hosein Mohimani, Tara Byrum, Pavel A. Pevzner, Pieter C. Dorrestein, Carmenza Spadafora, and William H. Gerwick. 2011. "Cyto-toxic Veraguamides, Alkynyl Bromide-Containing Cyclic Depsipeptides from the Marine Cyanobacterium Cf. Oscillatoria Margaritifera." *Journal of Natural Products* 74 (5): 928–936. https://doi.org/10.1021/np200077f.

Miao, Vivian, Renee Brost, Joanne Chapple, Kevin She, Marie-François Coëffet-Le Gal, and Richard H Baltz. 2006. "The Lipopeptide Antibiotic A54145 Biosynthetic Gene Cluster from Streptomyces Fradiae." *Journal of Industrial Microbiology and Biotechnology* 33 (2): 129–140. https://doi.org/10.1007/s10295-005-0028-5.

Mikkola, Raimo, Nils-Erik L. Saris, Pavel A. Grigoriev, Maria A. Andersson, and Mirja S. Salkinoja-Salonen. 1999. "Ionophoretic Properties and Mitochondrial Effects of Cereulide." *European Journal of Biochemistry* 263 (1): 112–117. https://doi.org/10.1046/j.1432-1327.1999.00476.x.

Milligan, Kenneth E., Brian L. Marquez, R. Thomas Williamson, and William H. Gerwick. 2000. "Lyngbyabellin B, a Toxic and Antifungal Secondary Metabolite from the Marine Cyanobacterium Lyngbya m Ajuscula." *Journal of Natural Products* 63 (10): 1440–1443. https://doi.org/10.1021/np000133y.

Miyashita, Masahiro, Tomoko Nakamori, Hisashi Miyagawa, Miki Akamatsu, and Tamio Ueno. 2003. "Inhibitory Activity of Analogues of AM-Toxin, a Host-Specific Phytotoxin from the Alternaria Alternata Apple Pathotype, on Photosynthetic O₂ Evolution in Apple Leaves." *Bioscience, Biotechnology, and Biochemistry* 67 (3): 635–638. https://doi.org/10.1271/bbb.67.635.

Moein, Mohammad Mahdi, Aziza El Beqqali, and Mohamed Abdel-Rehim. 2017. "Bioanalytical Method Development and Validation: Critical Concepts and Strategies." *Extraction and Sample Preparation Techniques in Bioanalysis* 1043 (February):3–11. https://doi.org/10.1016/j.jchromb.2016.09.028.

Montaser, Rana, Khalil A. Abboud, Valerie J. Paul, and Hendrik Luesch. 2011. "Pitiprolamide, a Proline-Rich Dolastatin 16 Analogue from the Marine Cyanobacterium Lyngbya majuscula from Guam." *Journal of Natural Products* 74 (1): 109–112. https://doi.org/10.1021/np1006839.

Montaser, Rana, Valerie J. Paul, and Hendrik Luesch. 2011. "Pitipeptolides C–F, Antimycobacterial Cyclodepsipeptides from the Marine Cyanobacterium Lyngbya majuscula from Guam." *Phytochemistry* 72 (16): 2068–2074. https://doi.org/10.1016/j.phytochem.2011.07.014.

Moore, Bradley S., Jacqueline A. Trischman, Dieter Seng, David Kho, Paul R. Jensen, and William Fenical. 1999. "Salinamides, Antiinflammatory Depsipeptides from a Marine Streptomy-cete." *The Journal of Organic Chemistry* 64 (4): 1145–1150. https://doi.org/10.1021/jo9814391.

More, Michelle B., Douglas Ray, and P. B. Armentrout. 1999. "Intrinsic Affinities of Alkali Cations for 15-Crown-5 and 18-Crown-6: Bond Dissociation Energies of Gas-Phase M⁺–Crown Ether
Complexes.” *Journal of the American Chemical Society* 121 (2): 417–423. https://doi.org/10.1021/ja9823159.

Morris, Howard R., Maria Panico, Michael Barber, Robert S. Bordoli, Robert D. Sedgwick, and Andrew Tyler. 1981. "Fast Atom Bombardment: A New Mass Spectrometric Method for Peptide Sequence Analysis." *Biochemical and Biophysical Research Communications* 101 (2): 623–631. https://doi.org/10.1016/0006-291X(81)91304-8.

Müller, Jane, Sven C. Feifel, Timo Schmiederer, Rainer Zocher, and Roderich D. Süssmuth. 2009. "In Vitro Synthesis of New Cyclodepsipeptides of the PF1022-Type: Probing the α-D-Hydroxy Acid Tolerance of PF1022 Synthetase." *ChemBioChem* 10 (2): 323–328. https://doi.org/10.1002/cbic.200800539.

Murray, Kermit K., Robert K. Boyd, Marcos N. Eberlin, G. John Langley, Liang Li, and Yasuhide Naito. 2013. "Definitions of terms relating to mass spectrometry (IUPAC Recommendations 2013)." *Pure and Applied Chemistry* 85 (7): 1515–1609. https://doi.org/10.1351/PAC-REC-06-04-06.

Nakamukai, Shohei, Kentaro Takada, Kazuo Furihata, Yuji Ise, Shigeru Okada, Yasuhiro Morii, Nobuhiro Yamawaki, et al. 2018. "Stellatolide H, a Cytotoxic Peptide Lactone from a Deep-Sea Sponge Discodermia Sp." *Tetrahedron Letters* 59 (26): 2532–2536. https://doi.org/10.1016/j.tetlet.2018.05.033.

Naranjo, María, Sarah Denayer, Nadine Botteldoorn, Laurence Delbrassinne, Jean Veys, Jacques Waegenaere, Nicolas Sirtaine, et al. 2011. "Sudden Death of a Young Adult Associated with Bacillus Cereus Food Poisoning." *Journal of Clinical Microbiology* 49 (12): 4379–4381. https://doi.org/10.1128/JCM.05129-11.

Newman, David J., and Gordon M. Cragg. 2004. "Marine Natural Products and Related Compounds in Clinical and Advanced Preclinical Trials." *Journal of Natural Products* 67 (8): 1216–1238. https://doi.org/10.1021/np040031y.

Ngoka, Lambert C. M., and Michael L. Gross. 1999. "A Nomenclature System for Labeling Cyclic Peptide Fragments." *Journal of the American Society for Mass Spectrometry* 10 (4): 360–363. https://doi.org/10.1016/S1044-0305(99)00006-9.

Ngoka, Lambert C. M., and Michael L Gross. 2000. "Multistep Collisionally Activated Decomposition in an Ion Trap for the Determination of the Amino-Acid Sequence and Gas-Phase Ion Chemistry of Lithium-Coordinated valinomycin11Dedicated to Professor Jim Morrison on the Occasion of His 75th Birthday." *International Journal of Mass Spectrometry* 194 (2): 247–259. https://doi.org/10.1016/S1387-3806(98)00192-X.

Ngoka, Lambert C. M., Michael L. Gross, and Peter L. Toogood. 1999. "Sodium-Directed Selective Cleavage of Lactones: A Method for Structure Determination of cyclodepsipeptides11Dedicated to the Memory of Professor Ben S. Freiser." *International Journal of Mass Spectrometry* 182–183: 289–298. https://doi.org/10.1016/S1387-3806(98)14248-3.

Nguyen, Kien T., Xiaowei He, Dylan C. Alexander, Chen Li, Jian-Qiao Gu, Carmela Mascio, Andrew Van Praagh, et al. 2010. "Genetically Engineered Lipopeptide Antibiotics Related to A54145 and Daptomycin with Improved Properties." *Antimicrobial Agents and Chemotherapy* 54 (4): 1404–1413. https://doi.org/10.1128/aac.01307-09.

Nold, Michael J., Blas A. Cerda, and Chrys Wesdemiotis. 1999. "Proton Affinities of the N- and C-Terminal Segments Arising

upon the Dissociation of the Amide Bond in Protonated Peptides." *Journal of the American Society for Mass Spectrometry* 10 (1): 1–8. https://doi.org/10.1016/S1044-0305(98)00120-2.

von Nussbaum, Franz, Michael Brands, Berthold Hinzen, Stefan Weigand, and Dieter Häbich. 2006. "Antibacterial Natural Products in Medicinal Chemistry—Exodus or Revival?" *Angewandte Chemie International Edition* 45 (31): 5072–5129. https://doi.org/10.1002/anie.200600350.

Oh, Dong-Chan, Paul R. Jensen, and William Fenical. 2006. "Zygosporamide, a Cytotoxic Cyclic Depsipeptide from the Marine-Derived Fungus Zygosporium Masonii." *Tetrahedron Letters* 47 (48): 8625–8628. https://doi.org/10.1016/j.tetlet.2006.08.113.

Oh, Dong-Chan, Christopher A. Kauffman, Paul R. Jensen, and William Fenical. 2007. "Induced Production of Emericellamides A and B from the Marine-Derived Fungus Emericella Sp. in Competing Co-Culture." *Journal of Natural Products* 70 (4): 515–520. https://doi.org/10.1021/np060381f.

Oh, Dong-Chan, Michael Poulsen, Cameron R. Currie, and Jon Clardy. 2009. "Dentigerumycin: A Bacterial Mediator of an Ant-Fungus Symbiosis." *Nature Chemical Biology* 5 (6): 391–393. https://doi.org/10.1038/nchembio.159.

Ohsawa, Kosuke, Sakiko Fukaya, and Takayuki Doi. 2022. "Total Synthesis and Structural Determination of Cyclodepsipeptide Decatransin." *Organic Letters* 24 (30): 5552–5556. https://doi.org/10.1021/acs.orglett.2c02085.

Ohyama, Makoto, Masaaki Takahashi, Yoshiya Shigematsu, Osamu Sakanaka, Yasushi Murai, and Katsuharu Inuma. 1999. Process for producing cyclodepsipeptide compounds and novel cyclodepsipeptide. China CN1230182A, filed August 7, 1997, and issued September 29, 1999. https://data.epo.org/publication-server/document?iDocId=1651368&iFormat=0.

Ojima, Daisuke, Ayano Yasui, Koh Tohyama, Keita Tokuzumi, Eisuke Toriihara, Kayoko Ito, Arihiro Iwasaki, Tomohiko Tomura, Makoto Ojika, and Kiyotake Suenaga. 2016. "Total Synthesis of Miuraenamides A and D." *The Journal of Organic Chemistry* 81 (20): 9886–9894. https://doi.org/10.1021/acs.joc.6b02061.

Okada, Yumika, Shigeki Matsunaga, Rob W. M. van Soest, and Nobuhiro Fusetani. 2002. "Nagahamide A, an Antibacterial Depsipeptide from the Marine Sponge Theonella Swinhoei1." *Organic Letters* 4 (18): 3039–3042. https://doi.org/10.1021/ol0262791.

Oku, Naoya, Kirk R. Gustafson, Laura K. Cartner, Jennifer A. Wilson, Nobuharu Shigematsu, Sonja Hess, Lewis K. Pannell, Michael R. Boyd, and James B. McMahon. 2004. "Neamphamide A, a New HIV-Inhibitory Depsipeptide from the Papua New Guinea Marine Sponge Neamphius Huxleyi." *Journal of Natural Products* 67 (8): 1407–1411. https://doi.org/10.1021/np040003f.

Olsen, Jesper V., Boris Macek, Oliver Lange, Alexander Makarov, Stevan Horning, and Matthias Mann. 2007. "Higher-Energy C-Trap Dissociation for Peptide Modification Analysis." *Nature Methods* 4 (9): 709–712. https://doi.org/10.1038/nmeth1060.

Paizs, Béla, and Sándor Suhai. 2002. "Combined Quantum Chemical and RRKM Modeling of the Main Fragmentation Pathways of Protonated GGG. II. Formation of B2, Y1, and Y2
Ions." *Rapid Communications in Mass Spectrometry* 16 (5): 375-389. https://doi.org/10.1002/rcm.586.

Paizs, Béla, and Sándor Suhai. 2005. "Fragmentation Pathways of Protonated Peptides." *Mass Spectrometry Reviews* 24 (4): 508-548. https://doi.org/10.1002/mas.20024.

Paulo, Bruno S., Renata Sigrist, Célio F. F. Angolini, and Luciana G. De Oliveira. 2019. "New Cyclodepsipeptide Derivatives Revealed by Genome Mining and Molecular Networking." *ChemistrySelect* 4 (27): 7785-7790. https://doi.org/10.1002/slct.201900922.

Pereira, Alban, Zhengyu Cao, Thomas F. Murray, and William H. Gerwick. 2009. "Hoiamide A, a Sodium Channel Activator of Unusual Architecture from a Consortium of Two Papua New Guinea Cyanobacteria." *Chemistry & Biology* 16 (8): 893-906. https://doi.org/10.1016/j.chembiol.2009.06.012.

Pettit, George R., John C. Knight, Delbert L. Herald, Robin K. Pettit, Fiona Hogan, Venugopal J. R. V. Mukku, John S. Hamblin, Michael J. II Dodson, and Jean-Charles Chapuis. 2009. "Antineoplastic Agents. 570. Isolation and Structure Elucidation of Bacillistatins 1 and 2 from a Marine Bacillus Silvestris." *Journal of Natural Products* 72 (3): 366-371. https://doi.org/10.1021/np800603u.

Pettit, George R., Rui Tan, Robin K. Pettit, Thomas H. Smith, Song Feng, Dennis L. Doubek, Linda Richert, John Hamblin, Christine Weber, and Jean-Charles Chapuis. 2007. "Antineoplastic Agents. 560. Isolation and Structure of Kitastatin 1 from an Alaskan Kitasatospora Sp." *Journal of Natural Products* 70 (7): 1069-1072. https://doi.org/10.1021/np068072c.

Pimentel-Elardo, Sheila Marie, Svitlana Kozytska, Tim S. Bugni, Chris M. Ireland, Heidrun Moll, and Ute Hentschel. 2010. "Anti-Parasitic Compounds from Streptomyces Sp. Strains Isolated from Mediterranean Sponges." *Marine Drugs* 8 (2): 373-380. https://doi.org/10.3390/md8020373.

Pitchayawasin, Suthasinee, Masaki Kuse, Kazushi Koga, Minoru Isobe, Norio Agata, and Michio Ohta. 2003. "Complexation of Cyclic Dodecadepsipeptide, Cereulide with Ammonium Salts." *Bioorganic & Medicinal Chemistry Letters* 13 (20): 3507-3512. https://doi.org/10.1016/S0960-894X(03)00731-5.

Plaza, Alberto, Giuseppe Bifulco, Jessica L. Keffer, John R. Lloyd, Heather L. Baker, and Carole A. Bewley. 2009. "Celebesidues A–C and Theopapuamides B–D, Depsipeptides from an Indonesian Sponge That Inhibit HIV-1 Entry." *The Journal of Organic Chemistry* 74 (2): 504–512. https://doi.org/10.1021/jo802232u.

Plaza, Alberto, Elena Gustchina, Heather L. Baker, Michelle Kelly, and Carole A. Bewley. 2007. "Mirabamides A–D, Depsipeptides from the Sponge Siliquariaspongia Mirabilis That Inhibit HIV-1 Fusion." *Journal of Natural Products* 70 (11): 1753-1760. https://doi.org/10.1021/np070306k.

Pohle, Stefan, Christian Appelt, Mallorie Roux, Hans-Peter Fiedler, and Roderich D. Süssmuth. 2011. "Biosynthetic Gene Cluster of the Non-Ribosomally Synthesized Cyclodepsipeptide Skyllamycin: Deciphering Unprecedented Ways of Unusual Hydroxylation Reactions." *Journal of the American Chemical Society* 133 (16): 6194-6205. https://doi.org/10.1021/ja108971p.

Polce, Michael J., Da Ren, and Chrys Wesdemiotis. 2000. "Disassociation of the Peptide Bond in Protonated Peptides." *Journal of*

Mass Spectrometry 35 (12): 1391-1398. https://doi.org/10.1002/1096-9888(200012)35:12<1391::AID-JMS85>3.0.CO;2-1.

Poli, Giulio, Romano Di Fabio, Luca Ferrante, Vincenzo Summa, and Maurizio Botta. 2017. "Largazole Analogues as Histone Deacetylase Inhibitors and Anticancer Agents: An Overview of Structure-Activity Relationships." *ChemMedChem* 12 (23): 1917-1926. https://doi.org/10.1002/cmdc.201700563.

Potterat, Olivier, Klaus Wagner, and Hubert Haag. 2000. "Liquid Chromatography–Electrospray Time-of-Flight Mass Spectrometry for on-Line Accurate Mass Determination and Identification of Cyclodepsipeptides in a Crude Extract of the Fungus Metarhizium Anisopliae." *Journal of Chromatography A* 872 (1): 85-90. https://doi.org/10.1016/S0021-9673(99)01268-6.

Qi, Na, Zhanlong Wang, Srinivasa Rao Allu, Qiang Liu, Jian Guo, and Yun He. 2016. "Total Syntheses of Anti-HIV Cyclodepsipeptides Aetheramides A and B." *The Journal of Organic Chemistry* 81 (24): 12466-12471. https://doi.org/10.1021/acs.joc.6b02292.

Raju, Ritesh, Zeinab G. Khalil, Andrew M. Piggott, Antje Blumenthal, Donald L. Gardiner, Tina S. Skinner-Adams, and Robert J. Capon. 2014. "Mollemycin A: An Antimalarial and Antibacterial Glyco-Hexadepsipeptide-Polyketide from an Australian Marine-Derived Streptomyces Sp. (CMB-M0244)." *Organic Letters* 16 (6): 1716-1719. https://doi.org/10.1021/ol5003913.

Rashid, Mohammad A., Kirk R. Gustafson, Laura K. Cartner, Nobuharu Shigematsu, Lewis K. Pannell, and Michael R. Boyd. 2001. "Microspinosamide, a New HIV-Inhibitory Cyclic Depsipeptide from the Marine Sponge Sidonops Microspinosa." *Journal of Natural Products* 64 (1): 117-121. https://doi.org/10.1021/np0002379.

Ravindra, Gudihal, Rappal. S. Ranganayaki, Srinivasa Raghothama, Mandayam C. Srinivasan, Richard D. Gilardi, Isabella L. Karle, and Padmanabhan Balaram. 2004. "Two Novel Hexadepsipeptides with Several Modified Amino Acid Residues Isolated from the Fungus Isaria." *Chemistry & Biodiversity* 1 (3): 489-504. https://doi.org/10.1002/cbdv.200490043.

Raymond, Kenneth N., Emily A. Dertz, and Sanggoo S. Kim. 2003. "Enterobactin: An Archetype for Microbial Iron Transport." *Proceedings of the National Academy of Sciences* 100 (7): 3584-3588. https://doi.org/10.1073/pnas.0630018100.

Reimann, Marcel, Louis P Sandjo, Luis Antelo, Eckhard Thines, Isabella Siepe, and Till Opatz. 2017. "A New Member of the Fusaricidin Family – Structure Elucidation and Synthesis of Fusaricidin E." *Beilstein Journal of Organic Chemistry* 13: 1430-1438. https://doi.org/10.3762/bjoc.13.140.

Renaud, Justin B., Megan J. Kelman, David R. McMullin, Ken K.-C. Yeung, and Mark W. Sumarah. 2017. "Application of C8 Liquid Chromatography-Tandem Mass Spectrometry for the Analysis of Enniatins and Bassianolides." *Journal of Chromatography A* 1508: 65-72. https://doi.org/10.1016/j.chroma.2017.05.070.

Ribeiro, Ricardo, Eugénia Pinto, Carla Fernandes, and Emília Sousa. 2022. "Marine Cyclic Peptides: Antimicrobial Activity and Synthetic Strategies." *Marine Drugs* 20 (6): 397. https://doi.org/10.3390/md20060397.

Robles-Bañuelos, Benjamín, Lorena María Durán-Riveroll, Edgar Rangel-López, Hugo Isidro Pérez-López, and Leticia González-Maya. 2022. "Marine Cyanobacteria as Sources of Lead Anticancer Compounds: A Review of Families of
Metabolites with Cytotoxic, Antiproliferative, and Anti-
neoplastic Effects." *Molecules* 27 (15): 4814. https://doi.org/
10.3390/molecules27154814.

Rodríguez-Carrasco, Yelko, Daniela Heilos, Lennart Richter, Roderich D. Süssmuth, Petra Heffeter, Michael Sulyok, Lukas Kenner, Walter Berger, and Rita Dornetshuber-Fleiss. 2016. "Mouse Tissue Distribution and Persistence of the Food-Born Fusariotoxins Enniatin B and Beauvericin." *Toxicology Letters* 247: 35-44. https://doi.org/10.1016/j.toxlet.2016.02.008.

Roepstorff, P., and J. Fohlman. 1984. "Proposal for a Common Nomenclature for Sequence Ions in Mass Spectra of Peptides." *Biomedical Mass Spectrometry* 11 (11): 601. https://doi.org/10.1002/bms.1200111109.

Röllgen, F. W. 1983. "Principles of Field Desorption Mass Spectrometry (Review)." In *Ion Formation from Organic Solids*, edited by Alfred Benninghoven, 25:2-13. Springer Series in Chemical Physics. Berlin, Heidelberg: Springer Berlin Heidelberg. https://doi.org/10.1007/978-3-642-87148-1_1.

Romero, Francisco, Fernando Espliego, Julia Pérez Baz, Teresa García De Quesada, Dolores Grávalos, Fernando De La Calle, and José Luis Fernández-Puentes. 1997. "Thiocoraline, a New Depsipeptide with Antitumor Activity Produced by a Marine Micromonospora. I. Taxonomy, Fermentation, Isolation, and Biological Activities." *The Journal of Antibiotics* 50 (9): 734-737. https://doi.org/10.7164/antibiotics.50.734.

Rose, Lars, and A.T.A. Jenkins. 2007. "The Effect of the Ionophore Valinomycin on Biomimetic Solid Supported Lipid DPPT/E/EPC Membranes." *Bioelectrochemistry* 70 (2): 387-393. https://doi.org/10.1016/j.bioelechem.2006.05.009.

Rouzeau-Szynalski, Katia, Katharina Stollewerk, Ute Messelhäusser, and Monika Ehling-Schulz. 2020. "Why Be Serious about Emetic Bacillus Cereus: Cereulide Production and Industrial Challenges." *Food Microbiology* 85: 103279. https://doi.org/10.1016/j.fm.2019.103279.

Russell, D. W., C. G. Macdonald, and J. S. Shannon. 1964. "The Structure of the Cyclohexadepsipeptide, Sporidesmolide III." *Tetrahedron Letters* 5 (38): 2759-2764. https://doi.org/10.1016/S0040-4039(00)71726-6.

Sabareesh, V., R. S. Ranganayaki, S. Raghothama, M. P. Bopanna, Hemalatha Balaram, M. C. Srinivasan, and P. Balaram. 2007. "Identification and Characterization of a Library of Micro-heterogeneous Cyclohexadepsipeptides from the Fungus Isaria." *Journal of Natural Products* 70 (5): 715-729. https://doi.org/10.1016/j.np060532e.

Salvador, Lilibeth A., Jason S. Biggs, Valerie J. Paul, and Hendrik Luesch. 2011. "Veraguamides A–G, Cyclic Hexadepsipeptides from a Dolastatin 16-Producing Cyanobacterium Symploca Cf. Hydnoides from Guam." *Journal of Natural Products* 74 (5): 917-927. https://doi.org/10.1012/np200076t.

Salvador, Lilibeth A., Kanchan Taori, Jason S. Biggs, Jean Jakoncic, David A. Ostrov, Valerie J. Paul, and Hendrik Luesch. 2013. "Potent Elastase Inhibitors from Cyanobacteria: Structural Basis and Mechanisms Mediating Cytoprotective and Anti-Inflammatory Effects in Bronchial Epithelial Cells." *Journal of Medicinal Chemistry* 56 (3): 1276-1290. https://doi.org/10.1021/jm3017305.

Sasaki, Toru, Masayuki Takagi, Takasi Yaguchi, Shinji Miyadoh, Tadaaki Okada, and Masao Koyama. 1992. "A New Anthelmintic

Cyclodepsipeptide, PF1022A." *The Journal of Antibiotics* 45 (5): 692-697. https://doi.org/10.7164/antibiotics.45.692.

Schmidt, Jennifer J., Yogan Khatri, Scott I. Brody, Catherine Zhu, Halina Pietraszkiewicz, Frederick A. Valeriote, and David H. Sherman. 2020. "A Versatile Chemoenzymatic Synthesis for the Discovery of Potent Cryptophycin Analogs." *ACS Chemical Biology* 15 (2): 524-532. https://doi.org/10.1021/acscchembio.9b00998.

Schoenian, Ilka, Michael Spiteller, Manoj Ghaste, Rainer Wirth, Hubert Herz, and Dieter Spiteller. 2011. "Chemical Basis of the Synergism and Antagonism in Microbial Communities in the Nests of Leaf-Cutting Ants." *Proceedings of the National Academy of Sciences* 108 (5): 1955-1960. https://doi.org/10.1073/pnas.1008441108.

Scholz-Schroeder, Brenda K., Jonathan D. Soule, and Dennis C. Gross. 2003. "The sypA, sypB, and sypC Synthetase Genes Encode Twenty-Two Modules Involved in the Nonribosomal Peptide Synthesis of Syringopeptin by Pseudomonas Syringae Pv. Syringae B301D." *Molecular Plant-Microbe Interactions* 16 (4): 271-280. https://doi.org/10.1094/MPMI.2003.16.4.271.

Scholz-Schroeder, Brenda K., Jonathan D. Soule, Shi-En Lu, Ingeborg Grgurina, and Dennis C. Gross. 2001. "A Physical Map of the Syringomycin and Syringopeptin Gene Clusters Localized to an Approximately 145-Kb DNA Region of Pseudomonas Syringae Pv. Syringae Strain B301D." *Molecular Plant-Microbe Interactions* 14 (12): 1426-1435. https://doi.org/10.1094/MPMI.2001.14.12.1426.

Scott, V R, R Boehme, and T R Matthews. 1988. "New Class of Antifungal Agents: Jaspplakinolide, a Cyclodepsipeptide from the Marine Sponge, Jaspis Species." *Antimicrobial Agents and Chemotherapy* 32 (8): 1154-1157. https://doi.org/10.1128/AAC.32.8.1154.

Seger, Christoph, Sonja Sturm, Hermann Stuppner, Tariq M. Butt, and Hermann Strasser. 2004. "Combination of a New Sample Preparation Strategy with an Accelerated High-Performance Liquid Chromatography Assay with Photodiode Array and Mass Spectrometric Detection for the Determination of Distruxins from Metarhizium Anisopliae Culture Broth." *Journal of Chromatography A* 1061 (1): 35-43. https://doi.org/10.1016/j.chroma.2004.10.063.

Seipke, Ryan F., Jörg Barke, Charles Brearley, Lionel Hill, Douglas W. Yu, Rebecca J. M. Goss, and Matthew I. Hutchings. 2011. "A Single Streptomyces Symbiont Makes Multiple Antifungals to Support the Fungus Farming Ant Acromyrmex Octospinosus." *PLOS ONE* 6 (8): e22028. https://doi.org/10.1371/journal.pone.0022028.

Shin, Hee Jae, Mohammad A. Rashid, Laura K. Cartner, Heidi R. Bokesch, Jennifer A. Wilson, James B. McMahon, and Kirk R. Gustafson. 2015. "Stellettapeptins A and B, HIV-Inhibitory Cyclic Depsipeptides from the Marine Sponge Stelletta Sp." *Tetrahedron Letters* 56 (28): 4215-4219. https://doi.org/10.1016/j.tetlet.2015.05.058.

Shiomi, Kazuro, Ryosuke Matsui, Atsuo Kakei, Yuichi Yamaguchi, Rokuro Masuma, Hiroko Hatano, Noriko Arai, et al. 2010. "Verticilide, a New Ryanodine-Binding Inhibitor, Produced by Verticillium Sp. FKI-1033." *The Journal of Antibiotics* 63 (2): 77-82. https://doi.org/10.1038/ja.2009.126.

Shiota, Mitsutaka, Keiko Saitou, Hiroshi Mizumoto, Masanori Matsusaka, Norio Agata, Masahiro Nakayama, Masayoshi
Kage, et al. 2010. "Rapid Detoxification of Cereulide in Bacillus Cereus Food Poisoning." *Pediatrics* 125 (4): e951-e955. https://doi.org/10.1542/peds.2009-2319.

Silber, Johanna, Birgit Ohlendorf, Antje Labes, Christian Näther, and Johannes F. Imhoff. 2013. "Calcaripeptides A–C, Cyclodepsipeptides from a Calcarisporium Strain." *Journal of Natural Products* 76 (8): 1461–1467. https://doi.org/10.1021/np400262t.

Šimčíková, Daniela, Petr Tůma, Alexandr Jegorov Jr., Petr Šimek, and Petr Heneberg. 2020. "Rapid Methods for the Separation of Natural Mixtures of Beauverolides, Cholesterol Acyl-transferase Inhibitors, Isolated from the Fungus Isaria Fumosorosea." *Journal of Separation Science* 43 (5): 962–969. https://doi.org/10.1002/jssc.201901084.

Simmons, T. Luke, Lisa M. Nogle, Joseph Media, Frederick A. Valeriote, Susan L. Mooberry, and William H. Gerwick. 2009. "Desmethoxymajusculamide C, a Cyanobacterial Depsipeptide with Potent Cytotoxicity in Both Cyclic and Ring-Opened Forms." *Journal of Natural Products* 72 (6): 1011–1016. https://doi.org/10.1021/np9001674.

Sivanathan, Sivatharushan, and Jürgen Scherkenbeck. 2014. "Cyclodepsipeptides: A Rich Source of Biologically Active Compounds for Drug Research." *Molecules* 19 (8): 12368–12420. https://doi.org/10.3390/molecules190812368.

Smolewski, Piotr, and Tadeusz Robak. 2017. "The Discovery and Development of Romidepsin for the Treatment of T-Cell Lymphoma." *Expert Opinion on Drug Discovery* 12 (8): 859–873. https://doi.org/10.1080/17460441.2017.1341487.

Snyder, Dalton T., Sophie R. Harvey, and Vicki H. Wysocki. 2022. "Surface-Induced Dissociation Mass Spectrometry as a Structural Biology Tool." *Chemical Reviews* 122 (8): 7442–7487. https://doi.org/10.1021/acs.chemrev.1c00309.

Song, Hyuk-Hwan, Hee-Seok Lee, and Chan Lee. 2011. "A New Cytotoxic Cyclic Pentadepsipeptide, Neo-N-Methylsansalvamide Produced by Fusarium Solani KCCM90040, Isolated from Potato." *Food Chemistry* 126 (2): 472–478. https://doi.org/10.1016/j.foodchem.2010.11.023.

Sørensen, Jens Laurids, Kristian Fog Nielsen, Peter Have Rasmussen, and Ulf Thrane. 2008. "Development of a LC-MS/MS Method for the Analysis of Enniatins and Beauvericin in Whole Fresh and Ensiled Maize." *Journal of Agricultural and Food Chemistry* 56 (21): 10439–10443. https://doi.org/10.1021/jf802038b.

Stachelhaus, Torsten, and Mohamed A. Marahiel. 1995. "Modular Structure of Genes Encoding Multifunctional Peptide Synthetases Required for Non-Ribosomal Peptide Synthesis." *FEMS Microbiology Letters* 125 (1): 3–14. https://doi.org/10.1111/j.1574-6968.1995.tb07328.x.

Suchowilska, Elżbieta, Wolfgang Kandler, Michael Sulyok, Marian Wiwart, and Rudolf Krska. 2010. "Mycotoxin Profiles in the Grain of Triticum Monococcum, Triticum Dicoccum and Triticum Spelta after Head Infection with Fusarium Culmorum." *Journal of the Science of Food and Agriculture* 90 (4): 556–565. https://doi.org/10.1002/jsfa.3844.

Sulyok, Michael, Franz Berthiller, Rudolf Krska, and Rainer Schuhmacher. 2006. "Development and Validation of a Liquid Chromatography/Tandem Mass Spectrometric Method for the Determination of 39 Mycotoxins in Wheat and Maize." *Rapid Communications in Mass Spectrometry* 20 (18): 2649–2659. https://doi.org/10.1002/rcm.2640.

Sun, Peng, Katherine N. Maloney, Sang-Jip Nam, Nina M. Haste, Ritesh Raju, William Aalbersberg, Paul R. Jensen, Victor Nizet, Mary E. Hensler, and William Fenical. 2011. "Fijimycins A–C, Three Antibacterial Etamycin-Class Depsipeptides from a Marine-Derived Streptomyces Sp." *Bioorganic & Medicinal Chemistry, Current Perspectives in Marine Bioorganic Chemistry*, 19 (22): 6557–6562. https://doi.org/10.1016/j.bmc.2011.06.053.

Suwan, Sathorn, Minoru Isobe, Ikuko Ohtani, Norio Agata, Masashi Mori, and Michio Ohta. 1995. "Structure of Cereulide, a Cyclic Dodecadepsipeptide Toxin from Bacillus Cereus and Studies on NMR Characteristics of Its Alkali Metal Complexes Including a Conformational Structure of the K+ Complex." *Journal of the Chemical Society, Perkin Transactions, 1* 765–775. https://doi.org/10.1039/P19950000765.

Suzuki, Akinori, Masaharu Kanaoka, Akira Isogai, Saburo Tamura, Shigeo Murakoshi, and Masakatsu Ichinoe. 1977. "Bassianolide, a New Insecticidal Cyclodepsipeptide from Beauveria Bassiana and Verticillium Lecanii." *Tetrahedron Letters* 18 (25): 2167–2170. https://doi.org/10.1016/S0040-4039(01)83709-6.

Sy-Cordero, Arlene A., Cedric J. Pearce, and Nicholas H. Oberlies. 2012. "Revisiting the Enniatins: A Review of Their Isolation, Biosynthesis, Structure Determination and Biological Activities." *The Journal of Antibiotics* 65 (11): 541–549. https://doi.org/10.1038/ja.2012.71.

Syka, John E. P., Joshua J. Coon, Melanie J. Schroeder, Jeffrey Shabanowitz, and Donald F. Hunt. 2004. "Peptide and Protein Sequence Analysis by Electron Transfer Dissociation Mass Spectrometry." *Proceedings of the National Academy of Sciences* 101 (26): 9528–9533. https://doi.org/10.1073/pnas.0402700101.

Tabet, Jean Claude., and Robert J. Cotter. 1984. "Laser Desorption Time-of-Flight Mass Spectrometry of High Mass Molecules." *Analytical Chemistry* 56 (9): 1662–1667. https://doi.org/10.1021/ac00273a028.

Tabet, Jean-Claude, Yves Gimbert, Annelaure Damont, David Touboul, François Fenaille, and Amina S. Woods. 2021. "Combining Chemical Knowledge and Quantum Calculation for Interpreting Low-Energy Product Ion Spectra of Metabolite Adduct Ions: Sodiated Diterpene Diester Species as a Case Study." *Journal of the American Society for Mass Spectrometry* 32 (10): 2499–2504. https://doi.org/10.1021/jasms.1c00154.

Taevernier, Lien, Evelien Wynendaele, Bert Gevaert, and De Bart Spiegeleer. 2017. "Chemical Classification of Cyclic Depsipeptides." *Current Protein & Peptide Science* 18 (5): 425–452. https://doi.org/10.2174/1389203717666161128141438.

Takabe, F., and M. Oya. 1976. "An Autopsy Case of Food Poisoning Associated with Bacillus Cereus." *Forensic Science* 7 (2): 97–101. https://doi.org/10.1016/0300-9432(76)90024-8.

Takesako, Kazutoh, Katsushige Ikai, Fumiyo Haruna, Masahiro Endo, Kazuo Shimanaka, Eiko Sono, Teruya Nakamura, Ikunoshin Kato, and Hideyo Yamaguchi. 1991. "Aureobasidins, New Antifungal Antibiotics. Taxonomy, Fermentation, Isolation, and Properties." *The Journal of Antibiotics* 44 (9): 919–924. https://doi.org/10.7164/antibiotics.44.919.

Tanabe, Koichi, Erwin Lamping, Kyoko Adachi, Yukie Takano, Kazutaka Kawabata, Yoshikazu Shizuri, Masakazu Niimi, and Yoshimasa Uehara. 2007. "Inhibition of Fungal ABC Transporters by Unnarmicin A and Unnarmicin C, Novel Cyclic Peptides from Marine Bacterium." *Biochemical and Biophysical Research*
Communications 364 (4): 990–995. https://doi.org/10.1016/j.bbrc.2007.10.110.

Taniguchi, Masatoshi, Joshawna K. Nunnery, Niclas Engene, Eduardo Esquenazi, Tara Byrum, Pieter C. Dorrestein, and William H. Gerwick. 2010. "Palmyramide A, a Cyclic Depsipeptide from a Palmyra Atoll Collection of the Marine Cyanobacterium Lyngbya majuscula." *Journal of Natural Products* 73 (3): 393–398. https://doi.org/10.1021/np900428h.

Temper, K. 1963. "Exitus Letalis Nach Lebensmittelvergiftung Durch Bazillus Cereus" 9: 481–490.

Terracciano, Stefania, Ines Bruno, Giuseppe Bifulco, Elvira Avallone, Charles D. Smith, Luigi Gomez-Paloma, and Raffaele Riccio. 2005. "Synthesis, Solution Structure, and Bioactivity of Six New Simplified Analogues of the Natural Cyclodepsipeptide Jasparomide." *Bioorganic & Medicinal Chemistry* 13 (17): 5225–5239. https://doi.org/10.1016/j.bmc.2005.05.042.

Thery, Marin, Vladimir L. Cousin, Pierre Tissieres, Maxime Enault, and Luc Morin. 2022. "Multi-Organ Failure Caused by Lasagnas: A Case Report of Bacillus Cereus Food Poisoning." *Frontiers in Pediatrics* 10: 978250. https://doi.org/10.3389/fped.2022.978250.

Tripathi, Ashootosh, Jonathan Puddick, Michele R. Prinsep, Peter Peng Foo Lee, and Lik Tong Tan. 2009. "Hantupeptin A, a Cytotoxic Cyclic Depsipeptide from a Singapore Collection of Lyngbya majuscula." *Journal of Natural Products* 72 (1): 29–32. https://doi.org/10.1021/np800448t.

Tripathi, Ashootosh, Jonathan Puddick, Michèle R. Prinsep, Matthias Rottmann, and Lik Tong Tan. 2010. "Lagunamides A and B: Cytotoxic and Antimalarial Cyclodepsipeptides from the Marine Cyanobacterium Lyngbya Majuscula." *Journal of Natural Products* 73 (11): 1810–1814. https://doi.org/10.1021/np100442x.

Uhlig, Silvio, and Lada Ivanova. 2004. "Determination of Beauvericin and Four Other Enniatins in Grain by Liquid Chromatography–Mass Spectrometry." *Journal of Chromatography A* 1050 (2): 173–178. https://doi.org/10.1016/j.chroma.2004.08.031.

Uhlig, Silvio, Lada Ivanova, Dirk Petersen, and Ralf Kristensen. 2009. "Structural Studies on Minor Enniatins from Fusarium Sp. VI 03441: Novel N-Methyl-Threonine Containing Enniatins." *Toxicon* 53 (7–8): 734–742. https://doi.org/10.1016/j.toxicon.2009.02.014.

Urbaniak, Monika, Łukasz Stępień, and Silvio Uhlig. 2019. "Evidence for Naturally Produced Beauvericins Containing N-Methyl-Tyrosine in Hypocreales Fungi." *Toxins* 11 (3): 182. https://doi.org/10.3390/toxins11030182.

Veld, P.H. in't, L.F.J. van der Laak, M. van Zon, and E.G. Biesta-Peters. 2019. "Elaboration and Validation of the Method for the Quantification of the Emetic Toxin of Bacillus Cereus as Described in EN-ISO 18465 - Microbiology of the Food Chain – Quantitative Determination of Emetic Toxin (Cereulide) Using LC-MS/MS." *European and International Validation of 15 Main Reference Methods in the Microbiology of the Food Chain* 288: 91–96. https://doi.org/10.1016/j.ijffoodmicro.2018.03.021.

Verekar, Shilpa Amit, Prabhu Dutt Mishra, Eyyammadichiyil Sankaranarayanan Sreekumar, Sunil Kumar Deshmukh, Heinz-Herbert Fiebig, Gerhard Kelter, and Armin Maier. 2014. "Anticancer Activity of New Depsipeptide Compound Isolated from an Endophytic Fungus." *The Journal of Antibiotics* 67 (10): 697–701. https://doi.org/10.1038/ja.2014.58.

Vongvanich, Namphung, Prasat Kittakoop, Masahiko Isaka, Srisuda Trakulnaleamsai, Saovaluk Vimuttipong, Morakot

Tanticharoen, and Yodhathai Thebtaranonth. 2002. "Hirsutellide A, a New Antimycobacterial Cyclohexadepsipeptide from the Entomopathogenic Fungus Hirsutella Kobayasii." *Journal of Natural Products* 65 (9): 1346–1348. https://doi.org/10.1021/np020055.

Vorm, Ole., Peter. Roepstorff, and Matthias. Mann. 1994. "Improved Resolution and Very High Sensitivity in MALDI TOF of Matrix Surfaces Made by Fast Evaporation." *Analytical Chemistry* 66 (19): 3281–3287. https://doi.org/10.1021/ac00091a044.

Walser, Veronika, Markus Kranzler, Corinna Dawid, Monika Ehling-Schulz, Timo D. Stark, and Thomas F. Hofmann. 2022. "Bacillus Cereus Toxin Repertoire: Diversity of (Iso)Cereulide(s)." *Molecules* 27 (3): 872. https://doi.org/10.3390/molecules27030872.

Walser, Veronika, Markus Kranzler, Monika Ehling-Schulz, Timo D. Stark, and Thomas F. Hofmann. 2021. "Structure Revision of Isocereulide A, an Isoform of the Food Poisoning Emetic Bacillus Cereus Toxin Cereulide." *Molecules* 26 (5): 1360. https://doi.org/10.3390/molecules26051360.

Walsh, Christopher T, Huawei Chen, Thomas A Keating, Brian K Hubbard, Heather C Losey, Lusong Luo, C. Gary Marshall, Deborah Ann Miller, and Hiten M Patel. 2001. "Tailoring Enzymes That Modify Nonribosomal Peptides during and after Chain Elongation on NRPS Assembly Lines." *Current Opinion in Chemical Biology* 5 (5): 525–534. https://doi.org/10.1016/S1367-5931(00)00235-0.

Wang, Lei, Nanxi Wang, Wenping Zhang, Xurui Cheng, Zhibin Yan, Gang Shao, Xi Wang, Rui Wang, and Caiyun Fu. 2022. "Therapeutic Peptides: Current Applications and Future Directions." *Signal Transduction and Targeted Therapy* 7 (1): 1–27. https://doi.org/10.1038/s41392-022-00904-4.

Wang, Nian, Shi-En Lu, Jianlin Wang, Z. Jeffrey Chen, and Dennis C. Gross. 2006. "The Expression of Genes Encoding Lipodepsipeptide Phytotoxins by Pseudomonas Syringae Pv. Syringae Is Coordinated in Response to Plant Signal Molecules." *Molecular Plant-Microbe Interactions* 19 (3): 257–269. https://doi.org/10.1094/MPMI-19-0257.

Wang, Nian, Shi-En Lu, Qingwu Yang, Sing-Hoi Sze, and Dennis C. Gross. 2006. "Identification of the Syr-Syp Box in the Promoter Regions of Genes Dedicated to Syringomycin and Syringopeptin Production by Pseudomonas Syringae Pv. Syringae B301D." *Journal of Bacteriology* 188 (1): 160–168. https://doi.org/10.1128/jb.188.1.160-168.2006.

Williams, Philip G., Wesley Y. Yoshida, Richard E. Moore, and Valerie J. Paul. 2002. "Isolation and Structure Determination of Obyanamide, a Novel Cytotoxic Cyclic Depsipeptide from the Marine Cyanobacterium Lyngbya confervoides." *Journal of Natural Products* 65 (1): 29–31. https://doi.org/10.1021/np0102253.

Williams, Philip G., Wesley Y. Yoshida, Richard E. Moore, and Valerie J. Paul. 2003. "Tasipeptins A and B: New Cytotoxic Depsipeptides from the Marine Cyanobacterium Sympleca Sp." *Journal of Natural Products* 66 (5): 620–624. https://doi.org/10.1021/np020582t.

Williams, Philip G., Wesley Y. Yoshida, Michael K. Quon, Richard E. Moore, and Valerie J. Paul. 2003a. "The Structure of Palau'amide, a Potent Cytotoxin from a Species of the Marine Cyanobacterium Lyngbya." *Journal of Natural Products* 66 (12): 1545–1549. https://doi.org/10.1021/np034001r.

Williams, Philip G., Wesley Y. Yoshida, Michael K. Quon, Richard E. Moore, and Valerie J. Paul. 2003b. "Ulongapeptin,
a Cytotoxic Cyclic Depsipeptide from a Palauan Marine Cyanobacterium Lyngbya Sp." *Journal of Natural Products* 66 (5): 651–654. https://doi.org/10.1021/np030050s.

Williams, Sheldon M., and Jennifer S. Brodbelt. 2004. "MSn Characterization of Protonated Cyclic Peptides and Metal Complexes." *Journal of the American Society for Mass Spectrometry* 15 (7): 1039–1054. https://doi.org/10.1016/j.jasms.2004.03.015.

Woods, Amina, Susanne Moyer, Hay-Yan Wang, and Roy Wise. 2003. "Interaction of Chlorisondamine with the Neuronal Nicotinic Acetylcholine Receptor." *Journal of Proteome Research* 2:207–212. https://doi.org/10.1021/pr025578h.

Woods, Amina S. 2004. "The Mighty Arginine, the Stable Quaternary Amines, the Powerful Aromatics, and the Aggressive Phosphate: Their Role in the Noncovalent Minuet." *Journal of Proteome Research* 3 (3): 478–484. https://doi.org/10.1021/pr034091l.

Woods, Amina S., and Sergi Ferré. 2005. "Amazing Stability of the Arginine–Phosphate Electrostatic Interaction." *Journal of Proteome Research* 4 (4): 1397–1402. https://doi.org/10.1021/pr050077s.

Woods, Amina S., and Shelley N. Jackson. 2013. "How Adenylate Cyclase Choreographs the Pas de Deux of the Receptors Heteromerization Dance." *Neuroscience* 238: 335–344. https://doi.org/10.1016/j.neuroscience.2013.02.006.

Wu, Hui-Fen, Suresh Kumar Kailasin, and Chi-Hsien Lin. 2011. "Single Drop Microextraction Coupled with Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry for Rapid and Direct Analysis of Hydrophobic Peptides from Biological Samples in High Salt Solution." *Rapid Communications in Mass Spectrometry* 25 (2): 307–315. https://doi.org/10.1002/rcm.4843.

Wulfson, N. S., V. A. Puchkov, V. N. Bochkarev, B. V. Rozinov, A. M. Zyakoon, M. M. Shemyakin, Yu. A. Ovchinnikov, et al. 1964. "Mass Spectrometric Study of Cyclodepsipeptides." *Tetrahedron Letters* 5 (17): 951–960. https://doi.org/10.1016/S0040-4039(00)90413-1.

Wulfson, N. S., V. A. Puchkov, B. V. Rozinov, A. M. Zyakoon, M. M. Shemyakin, Yu. A. Ovchinnikov, A. A. Kiryushkin, and V. T. Ivanov. 1965. "Mass Spectrometric Study of Cyclodepsipeptides. Fragmentation Types of Regular and Irregular Cyclohexadepsipeptides." *Tetrahedron Letters* 6 (32): 2793–2804. https://doi.org/10.1016/S0040-4039(01)83912-5.

Xu, Yuquan, Jixun Zhan, E. M. Kithsiri Wijeratne, Anna M. Burns, A. A. Leslie Gunatilaka, and István Molnár. 2007. "Cytotoxic and Antihaptotactic Beauvericin Analogues from Precursor-Directed Biosynthesis with the Insect Pathogen Beauveria Bassiana ATCC 7159." *Journal of Natural Products* 70 (9): 1467–1471. https://doi.org/10.1021/np070262f.

Yalcin, Talat, and Alex G. Harrison. 1996. "Ion Chemistry of Protonated Lysine Derivatives." *Journal of Mass Spectrometry* 31 (11): 1237–1243. https://doi.org/10.1002/(SICI)1096-9888(199611)31:11<1237::AID-JMS416>3.0.CO;2-P.

Yalcin, Talat, Charlotte Khouw, Imre G. Csizmadia, Michael R. Peterson, and Alex G. Harrison. 1995. "Why Are B Ions Stable Species in Peptide Spectra?" *Journal of the American Society for Mass Spectrometry* 6 (12): 1165–1174. https://doi.org/10.1016/1044-0305(95)00569-2.

Yamaguchi, Mizuka, Takao Kawai, Mikiya Kitagawa, and Yuko Kumeda. 2013. "A New Method for Rapid and Quantitative Detection of the Bacillus Cereus Emetic Toxin Cereulide in Food Products by Liquid Chromatography-Tandem Mass

Spectrometry Analysis." *Food Microbiology* 34 (1): 29–37. https://doi.org/10.1016/j.fm.2012.11.010.

Yamano, Yoshi, Masayoshi Arai, and Motomasa Kobayashi. 2012. "Neamphamide B, New Cyclic Depsipeptide, as an Anti-Dormant Mycobacterial Substance from a Japanese Marine Sponge of Neamphius Sp." *Bioorganic & Medicinal Chemistry Letters* 22 (14): 4877–4881. https://doi.org/10.1016/j.bmcl.2012.05.071.

Yamashita, Masamichi, and John B. Fenn. 1984. "Electrospray Ion Source. Another Variation on the Free-Jet Theme." *The Journal of Physical Chemistry* 88 (20): 4451–4459. https://doi.org/10.1021/j150664a002.

Yang, Shuo, Yating Wang, Yangtai Liu, Kai Jia, Zhen Zhang, and Qingli Dong. 2023. "Cereulide and Emetic Bacillus Cereus: Characterizations, Impacts and Public Precautions." *Foods* 12 (4): 833. https://doi.org/10.3390/foods12040833.

Yeh, Sheau Farn, Wei Pan, Geok-Toh Ong, Aih-Jing Chiou, Chy-Chong Chuang, Shyh-Horng Chiou, and Shih-Hsiung Wu. 1996. "Study of Structure-Activity Correlation in Destruxins, a Class of Cyclodepsipeptides Possessing Suppressive Effect on the Generation of Hepatitis B Virus Surface Antigen in Human Hepatoma Cells." *Biochemical and Biophysical Research Communications* 229 (1): 65–72. https://doi.org/10.1006/bbrc.1996.1758.

Yost, R. A., and C. G. Enke. 1979. "Triple Quadrupole Mass Spectrometry for Direct Mixture Analysis and Structure Elucidation." *Analytical Chemistry* 51 (12): 1251–1264. https://doi.org/10.1021/ac50048a002.

Yu, Mingming, Lilibeth A. Salvador, Sherwin K. B. Sy, Yufei Tang, Ravi S. P. Singh, Qi-Yin Chen, Yanxia Liu, Jiyong Hong, Hartmut Derendorf, and Hendrik Luesch. 2014. "Largazole Pharmacokinetics in Rats by LC-MS/MS." *Marine Drugs* 12 (3): 1623–1640. https://doi.org/10.3390/md12031623.

Zampella, Angela, M. Valeria D'Auria, Luigi Gomez Paloma, Agostino Casapullo, Luigi Minale, Cécile Debitus, and Yvette Henin. 1996. "Callipeltin A, an Anti-HIV Cyclic Depsipeptide from the New Caledonian Lithistida Sponge Callipelta Sp." *Journal of the American Chemical Society* 118 (26): 6202–6209. https://doi.org/10.1021/ja954287p.

Zampella, Angela, Valentina Sepe, Paolo Luciano, Filomena Bellotta, Maria Chiara Monti, Maria Valeria D'Auria, Trine Jepsen, et al. 2008. "Homophymine A, an Anti-HIV Cyclodepsipeptide from the Sponge Homophymia Sp." *The Journal of Organic Chemistry* 73 (14): 5319–5327. https://doi.org/10.1021/jo800583b.

Zan, Jindong, Zhiyuan Li, Ma. Diarey Tianero, Jeanette Davis, Russell T. Hill, and Mohamed S. Donia. 2019. "A Microbial Factory for Defensive Kahalalides in a Tripartite Marine Symbiosis." *Science* 364 (6445): eaaw6732. https://doi.org/10.1126/science.aaw6732.

Zeng, Mingyuan, Jianyun Tao, Shuang Xu, Xuelian Bai, and Huawei Zhang. 2023. "Marine Organisms as a Prolific Source of Bioactive Depsipeptides." *Marine Drugs* 21 (2): 120. https://doi.org/10.3390/md21020120.

Zhang, Songya, Jing Zhu, David L. Zechel, Claudia Jessen-Trefzer, Richard T. Eastman, Thomas Paululat, and Andreas Bechthold. 2018. "New WS9326A Derivatives and One New Annimycin Derivative with Antimalarial Activity Are Produced by Streptomyces Asterosporus DSM 41452 and Its Mutant." *ChemBioChem* 19 (3): 272–279. https://doi.org/10.1002/cbic.201700428.

Zöllner, Peter, and Bernhard Mayer-Helm. 2006. "Trace Mycotoxin Analysis in Complex Biological and Food Matrices by Liquid
Chromatography-Atmospheric Pressure Ionisation Mass Spectrometry.” *Journal of Chromatography A* 1136 (2): 123-169. https://doi.org/10.1016/j.chroma.2006.09.055.

Zuberovic Muratovic, Aida, Rikard Tröger, Kristina Granelli, and Karl-Erik Hellenäs. 2014. "Quantitative Analysis of Cereulide Toxin from Bacillus Cereus in Rice and Pasta Using Synthetic Cereulide Standard and 13C6-Cereulide Standard—A Short Validation Study." *Toxins* 6 (12): 3326-3335. https://doi.org/10.3390/toxins6123326.

## AUTHOR BIOGRAPHIES

<figure><img src="image_38.png" /></figure>

**Sophie Liuu** earned her PhD in 2014 in proteomics and mass spectrometry from ESPCI Paris/CNRS/Sorbonne university (France) under the supervision of Dr Joëlle Vinh. She is currently a project manager at the French Agency for Food, Environmental and Occupational Health & Safety (ANSES). Her research focuses on the structural characterization of cyclodepsipeptide toxins from Bacillus cereus, and enterotoxins from Bacillus cereus and Clostridium perfringens, both responsible for foodborne outbreaks worlwide, using high resolution mass spectrometry-based methods.

<figure><img src="image_39.png" /></figure>

**Annelaure Damont** received her PhD in 2006 in organic chemistry from the University of Montpellier II (France) for her R&D work within Idenix Pharmaceuticals. In 2015, she has joined the Laboratory of innovations in mass spectrometry for health (LI-MS) to integrate chemical approaches and isotopic labeling with metabolomics analysis by LC-HRMS. The implementation of novel methodologies for the large-scale quantification of metabolites and for the structural characterization of the unknown metabolome are her main areas of interest. She has been carrying out isotope-assisted research for over 20 years and is part of the national infrastructure in metabolomics and fluxomics, MetaboHub.

<figure><img src="image_40.png" /></figure>

**Alain Perret** obtained his PhD in Biochemistry at the University of Orsay (Paris-Saclay, France) under the supervision of Dr Denis Pompon. As a senior researcher at Genoscope, his research focuses on the experimental study of bacterial metabolism through combined approaches (LC-MS-based metabolomics and enzymology). More specifically, he is deeply involved in the structural elucidation of novel metabolites, the characterization

of new enzymatic reactions and the completion and discovery of metabolic pathways.

<figure><img src="image_41.png" /></figure>

**Olivier Firmesse**, PhD (2007), has joined ANSES as a research project leader in January 2007. He has over 10 years of experience in microbial ecophysiology and surface hygiene. Currently he is team leader and deputy head of the *Staphylococcus, Bacillus & Clostridium* (SBCL) unit of the ANSES Laboratory for Food Safety. The team's topic is the development of analytical tools for detection and characterisation of food pathogens belonging to the *Bacillus* and *Clostridium* genera responsible for foodborne outbreaks.

<figure><img src="image_42.png" /></figure>

**François Becher** earned a Doctor of Pharmacy degree and a Master degree in Analytical Chemistry in 1999, from Paris University, France. He received his PhD in Analytical Chemistry in 2002 at the Pharmacology and Immunology Unit, CEA Saclay and Paris University. Currently, he is a senior researcher at the Laboratory of Innovations in Mass Spectrometry (LI-MS) at CEA. His research focuses on mass spectrometry of biological toxins and protein biomarkers in CBRN and biomedical applications.

<figure><img src="image_43.png" /></figure>

**Gwenaëlle Lavison-Bompard** received her PhD in analytical chemistry from Paris Sorbonne University in 2004. Her research focusses on separation sciences, automation and hyphenations in the field of environment and food analysis, mostly dedicated to pesticides and toxins analysis in complex matrixes. Her activities include chromatographic and mass spectrometry methods development to improve their performances, from identification to quantification to ensure the robustness of the analytical results. She is also involved in normalization and accreditation bodies.

<figure><img src="image_44.png" /></figure>

**Amandine Hueber** received her PhD in analytical chemistry and mass spectrometry at INSERM, working on the structural identification of lipopeptides from gut microbiota (*Escherichia coli* and *Ligilactobacillus animalis*) in Metatoul-Lipidomic Facilities, with N. CENAC and J. BE-TRAND-MICHEL. She has expertise in developing analytical methods by LC-HRMS, and structural
characterization. Her research interests focus on developing techniques to obtain interoperable non-resonant collisional spectra in metabolomics.

<figure><img src="image_45.png" /></figure>

**Amina S. Woods** earned her PhD in Pharmacology and Molecular Sciences at Johns Hopkins University School of Medicine, characterizing Herpes viruses Assembly protein. She worked in Oncology Immunology sequencing MHC class1 and Ib peptides, and the first non-peptide ligand of CD1d1. She next defined the epitopes involved in GPCR heteromerizations and interactions. Then using a decoy peptide (DP) she blocked NMDAR mediated dynorphin neurotoxicity and neuronal cell death in concussion induced TBI and developed Imaging MS methodology to study brain tissue lipids in health and disease.

<figure><img src="image_46.png" /></figure>

**Ekaterina Darii** received her PhD in Chemistry at the Institute of Molecular Biology (Russian Academy of Sciences) in Moscow. She is currently a research engineer at Genoscope/CEA. Her activities include the development of analytical methods based on mass spectrometry techniques for metabolomics as well as structural studies of compounds of interest. Her particular interest focuses on exploring fragmentation mechanism by application of various instrument parameters, especially for studying the impact of stereochemistry on fragmentation orientation.

<figure><img src="image_47.png" /></figure>

**François Fenaille** received his diploma degree (1998) in analytical chemistry from the University of Nantes (France) and his PhD degree (2004) in analytical chemistry and mass spectrometry from Pierre & Marie Curie University (Paris,

France). In 2016, he became the head of Laboratory of Innovations in Mass Spectrometry for Health (LI-MS) at CEA. His current research is dedicated to the development of innovative mass spectrometry-based methods for metabolomics/lipidomics, targeted proteomics and glycomics applications, essentially in the field of biomarker discovery.

<figure><img src="image_48.png" /></figure>

**Emeritus Professor Jean-Claude Tabet** earned his PhD in 1973 in Chemistry (mass spectrometry) at the Orsay university and the Polytechnic school (Paris-Saclay). After postdoc positions at EPFL (Switzerland) and John Hopkins (Baltimore), he was nominated as Professor in organic chemistry and in mass spectrometry at Sorbonne university (Paris). He develops studies in stereochemistry and chirality through ion/molecule reactions, ion beam and ion storage instrumentation, internal energy, ion dissociation mechanisms, application in metabolomics and databank. Since 2011, he was detached to the CEA/LI-MS lab. He has transferred his knowledge through his MS courses in various French universities, and in overseas countries (Vietnam, India, Switzerland, Italy, China, Serbia, Israel and Algeria).

**How to cite this article:** Liuu S, Damont A, Perret A, et al. Origin and Characterization of Cyclodepsipeptides: Comprehensive Structural Approaches with Focus on Mass Spectrometry Analysis of Alkali-cationized Molecular Species. *Mass Spectrometry Reviews*, (2024);1–86.
https://doi.org/10.1002/mas.21904